Andrei Iagaru

All Publications

• Same-day post-therapy imaging with a new generation whole-body digital SPECT/CT in assessing treatment response to [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer. European journal of nuclear medicine and molecular imaging Song, H., Leonio, M. I., Ferri, V., Duan, H., Aparici, C. M., Davidzon, G., Franc, B. L., Moradi, F., Shah, J., Bergstrom, C. P., Fan, A. C., Shah, S., Khaki, A. R., Srinivas, S., Iagaru, A. 2024

  Abstract

  PURPOSE: Lutetium-177 [177Lu]Lu-PSMA-617 radioligand therapy (RLT) represents a significant advancement for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improvements in radiographic progression free survival (rPFS) and overall survival (OS) with a low rate of associated side effects. Currently, most post-therapy SPECT/CT is conducted at 24h after infusion. This study examines the clinical utility of a next-generation multi-detector Cadmium-Zinc-Telluride (CZT) SPECT/CT system (StarGuide) in same-day post-infusion assessment and early treatment response to [177Lu]Lu-PSMA-617.METHODS: In this retrospective study, 68 men with progressive mCRPC treated with [177Lu]Lu-PSMA-617 at our center from June 2022 to June 2023 were evaluated. Digital whole-body SPECT/CT imaging was performed after [177Lu]Lu-PSMA-617infusion (mean±SD: 1.8±0.6h, range 1.1-4.9h). Quantitative analysis of [177Lu]Lu-PSMA-617 positive lesions was performed in patients who underwent at least 2 post-therapy SPECT/CT, using liver parenchyma uptake as reference. Metrics including [177Lu]Lu-PSMA-617 positive total tumor volume (Lu-TTV), SUVmax and SUVmean were calculated. These quantitative metrics on post-infusion SPECT/CT images after cycles 1, 2 and 3 were correlated with overall survival (OS), prostate specific antigen-progression free survival (PSA-PFS) as defined by prostate cancer working group 3 (PCWG3), and PSA decrease over 50% (PSA50) response rates.RESULTS: 56 patients (means age 76.2±8.1 years, range: 60-93) who underwent at least 2 post-therapy SPECT/CT were included in the image analysis. The whole-body SPECT/CT scans (~12min per scan) were well tolerated, with 221 same-day scans performed (89%). At a median of 10-months follow-up, 33 (58.9%) patients achieved PSA50 after [177Lu]Lu-PSMA-617 treatment and median PSA-PFS was 5.0 months (range: 1.0-15 months) while median OS was not reached. Quantitative analysis of SPECT/CT images showed that 37 patients (66%) had>30% reduction in Lu-TTV, associated with significantly improved overall survival (median not reached vs. 6 months, P=0.008) and PSA-PFS (median 6 months vs. 1 months, P<0.001). However, changes in SUVmax or SUVmean did not correlate with PSA-PFS or OS.CONCLUSION: We successfully implemented same-day post-therapy SPECT/CT after [177Lu]Lu-PSMA-617 infusions. Quantitation of 1-2h post-therapy SPECT/CT images is a promising method for assessing treatment response. However, the approach is currently limited by its suboptimal detection of small tumor lesions and the necessity of incorporating a third-cycle SPECT/CT to mitigate the effects of any potential treatment-related flare-up. Further investigation in a larger patient cohort and prospective validation is essential to confirm these findings and to explore the role of SPECT/CT as a potential adjunct to PSMA PET/CT in managing mCRPC.

  View details for DOI 10.1007/s00259-024-06718-6

  View details for PubMedID 38635050

• The Age of Theragnostics. PET clinics Iagaru, A., Jacene, H. 2024

  View details for DOI 10.1016/j.cpet.2024.03.007

  View details for PubMedID 38594141

• Guiding principles on the education and practice of theranostics. European journal of nuclear medicine and molecular imaging Pascual, T. N., Paez, D., Iagaru, A., Gnanasegaran, G., Lee, S. T., Sathekge, M., Buatti, J. M., Giammarile, F., Al-Ibraheem, A., Pardo, M. A., Baum, R. P., De Bari, B., Ben-Haim, S., Blay, J. Y., Brink, A., Estrada-Lobato, E., Fanti, S., Golubic, A. T., Hatazawa, J., Israel, O., Kiess, A., Knoll, P., Louw, L., Mariani, G., Mirzaei, S., Orellana, P., Prior, J. O., Urbain, J. L., Vichare, S., Vinjamuri, S., Virgolini, I., Scott, A. M. 2024

  Abstract

  The recent development and approval of new diagnostic imaging and therapy approaches in the field of theranostics have revolutionised nuclear medicine practice. To ensure the provision of these new imaging and therapy approaches in a safe and high-quality manner, training of nuclear medicine physicians and qualified specialists is paramount. This is required for trainees who are learning theranostics practice, and for ensuring minimum standards for knowledge and competency in existing practising specialists.To address the need for a training curriculum in theranostics that would be utilised at a global level, a Consultancy Meeting was held at the IAEA in May 2023, with participation by experts in radiopharmaceutical therapy and theranostics including representatives of major international organisations relevant to theranostics practice.Through extensive discussions and review of existing curriculum and guidelines, a harmonised training program for theranostics was developed, which aims to ensure safe and high quality theranostics practice in all countries.The guiding principles for theranostics training outlined in this paper have immediate relevance for the safe and effective practice of theranostics.

  View details for DOI 10.1007/s00259-024-06657-2

  View details for PubMedID 38453729

  View details for PubMedCentralID 7367151

• Molecular Imaging in Soft-tissue Sarcoma: Evolving Role of FDG PET. Seminars in nuclear medicine Guja, K. E., Ganjoo, K. N., Iagaru, A. 2024

  Abstract

  Soft tissue sarcomas are a rare and heterogenous group of tumors that account for 2% of all cancer-related deaths. Molecular imaging with FDG PET can offer valuable metabolic information to help inform clinical management of soft tissue sarcomas that is unique and complementary to conventional diagnostic imaging techniques. FDG PET imaging often correlates with tumor grade, can help guide biopsy, and frequently detects additional sites of disease compared to conventional imaging in patients being considered for definitive or salvage therapy. Traditional size-based evaluation of treatment response is often inadequate in soft tissue sarcoma and changes in metabolic activity can add significant value to interim and end of treatment imaging for high-grade sarcomas. FDG PET can be used for detection of recurrence or malignant transformation and thus play a vital role in surveillance. This article reviews the evolving role of FDG PET in initial diagnosis, staging, treatment response assessment, and restaging. Further studies on the use of FDG PET in soft sarcoma are needed, particularly for rare histopathologic subtypes.

  View details for DOI 10.1053/j.semnuclmed.2024.02.001

  View details for PubMedID 38433024

• 68Ga-RM2 PET-MRI versus MRI alone for evaluation of patients with biochemical recurrence of prostate cancer: a single-centre, single-arm, phase 2/3 imaging trial. The Lancet. Oncology Duan, H., Moradi, F., Davidzon, G. A., Liang, T., Song, H., Loening, A. M., Vasanawala, S., Srinivas, S., Brooks, J. D., Hancock, S., Iagaru, A. 2024

  Abstract

  National Comprehensive Cancer Network guidelines include prostate-specific membrane antigen (PSMA)-targeted PET for detection of biochemical recurrence of prostate cancer. However, targeting a single tumour characteristic might not be sufficient to reflect the full extent of disease. Gastrin releasing peptide receptors (GRPR) have been shown to be overexpressed in prostate cancer. In this study, we aimed to evaluate the diagnostic performance of the GRPR-targeting radiopharmaceutical 68Ga-RM2 in patients with biochemical recurrence of prostate cancer.This single-centre, single-arm, phase 2/3 trial was done at Stanford University (USA). Adult patients (aged ≥18 years) with biochemical recurrence of prostate cancer, a Karnofsky performance status of 50 or higher, increasing prostate-specific antigen concentration 0·2 ng/mL or more after prostatectomy or 2 ng/mL or more above nadir after radiotherapy, and non-contributory conventional imaging (negative CT or MRI, and bone scan) were eligible. All participants underwent 68Ga-RM2 PET-MRI. The primary outcome was the proportion of patients with PET-positive findings on 68Ga-RM2 PET-MRI compared with MRI alone after initial therapy, at a per-patient and per-lesion level. The primary outcome would be considered met if at least 30% of patients had one or more lesions detected by 68Ga-RM2 PET-MRI and the detection by 68Ga-RM2 PET-MRI was significantly greater than for MRI. Each PET scan was interpreted by three independent masked readers using a standardised evaluation criteria. This study is registered with ClinicalTrials.gov, NCT02624518, and is complete.Between Dec 12, 2015, and July 27, 2021, 209 men were screened for eligibility, of whom 100 were included in analyses. Median follow-up was 49·3 months (IQR 36·7-59·2). The primary endpoint was met; 68Ga-RM2 PET-MRI was positive in 69 (69%) patients and MRI alone was positive in 40 (40%) patients (p<0·0001). In the per-lesion analysis 68Ga-RM2 PET-MRI showed significantly higher detection rates than MRI alone (143 vs 96 lesions; p<0·0001). No grade 1 or worse events were reported.68Ga-RM2 PET-MRI showed better diagnostic performance than MRI alone in patients with biochemical recurrence of prostate cancer. Further prospective comparative studies with PSMA-targeted PET are needed to gain a better understanding of GRPR and PSMA expression patterns in these patients.The US Department of Defense.

  View details for DOI 10.1016/S1470-2045(24)00069-X

  View details for PubMedID 38423030

• Nuclear Medicine and Molecular Imaging Applications in Gynecologic Malignancies: A Comprehensive Review. Seminars in nuclear medicine Khessib, T., Jha, P., Davidzon, G. A., Iagaru, A., Shah, J. 2024

  Abstract

  Gynecologic malignancies, consisting of endometrial, cervical, ovarian, vulvar, and vaginal cancers, pose significant diagnostic and management challenges due to their complex anatomic location and potential for rapid progression. These tumors cause substantial morbidity and mortality, often because of their delayed diagnosis and treatment. An estimated 19% of newly diagnosed cancers among women are gynecologic in origin. In recent years, there has been growing evidence supporting the integration of nuclear medicine imaging modalities in the diagnostic work-up and management of gynecologic cancers. The sensitivity of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) combined with the anatomical specificity of computed tomography (CT) and magnetic resonance imaging (MRI) allows for the hybrid evaluation of metabolic activity and structural abnormalities that has become an indispensable tool in oncologic imaging. Lymphoscintigraphy, using technetium 99m (99mTc) based radiotracers along with single photon emission computed tomography/ computed tomography (SPECT/CT), holds a vital role in the identification of sentinel lymph nodes to minimize the surgical morbidity from extensive lymph node dissections. While not yet standard for gynecologic malignancies, promising therapeutic nuclear medicine agents serve as specialized treatment options for patients with advanced or recurrent disease. This article aims to provide a comprehensive review on the nuclear medicine applications in gynecologic malignancies through the following objectives: 1) To describe the role of nuclear medicine in the initial staging, lymph node mapping, response assessment, and recurrence/surveillance imaging of common gynecologic cancers, 2) To review the limitations of 18F-FDG PET/CT and promising applications of 18F-FDG PET/MRI in gynecologic malignancy, 3) To underscore the promising theragnostic applications of nuclear medicine, 4) To highlight the current role of nuclear medicine imaging in gynecologic cancers as per the National Comprehensive Cancer Network (NCCN), European Society of Surgical Oncology (ESGO), and European Society of Medical Oncology (ESMO) guidelines.

  View details for DOI 10.1053/j.semnuclmed.2024.01.003

  View details for PubMedID 38342655

• Reply to Perera Molligoda Arachchige AS [1] CLINICAL AND TRANSLATIONAL IMAGING Laudicella, R., Davidzon, G. A., Dimos, N., Provenzano, G., Iagaru, A., Bisdas, S. 2024; 12 (1): 109-110

  View details for DOI 10.1007/s40336-023-00597-x

  View details for Web of Science ID 001151700500009

• Imaging GRPr Expression in Metastatic Castration-Resistant Prostate Cancer with [68Ga]Ga-RM2-A Head-to-Head Pilot Comparison with [68Ga]Ga-PSMA-11. Cancers Fernandez, R., Soza-Ried, C., Iagaru, A., Stephens, A., Muller, A., Schieferstein, H., Sandoval, C., Amaral, H., Kramer, V. 2023; 16 (1)

  Abstract

  BACKGROUND: The gastrin-releasing peptide receptor (GRPr) is highly overexpressed in several solid tumors, including treatment-naive and recurrent prostate cancer. [68Ga]Ga-RM2 is a well-established radiotracer for PET imaging of GRPr, and [177Lu]Lu-RM2 has been proposed as a therapeutic alternative for patients with heterogeneous and/or low expression of PSMA. In this study, we aimed to evaluate the expression of GRPr and PSMA in a group of patients diagnosed with castration-resistant prostate cancer (mCRPC) by means of PET imaging.METHODS: Seventeen mCRPC patients referred for radio-ligand therapy (RLT) were enrolled and underwent [68Ga]Ga-PSMA-11 and [68Ga]Ga-RM2 PET/CT imaging, 8.8 ± 8.6 days apart, to compare the biodistribution of each tracer. Uptake in healthy organs and tumor lesions was assessed by SUV values, and tumor-to-background ratios were analyzed.RESULTS: [68Ga]Ga-PSMA-11 showed significantly higher uptake in tumor lesions in bone, lymph nodes, prostate, and soft tissues and detected 23% more lesions compared to [68Ga]Ga-RM2. In 4/17 patients (23.5%), the biodistribution of both tracers was comparable.CONCLUSIONS: Our results show that in our cohort of mCRPC patients, PSMA expression was higher compared to GRPr. Nevertheless, RLT with [177Lu]Lu-RM2 may be an alternative treatment option for selected patients or patients in earlier disease stages, such as biochemical recurrence.

  View details for DOI 10.3390/cancers16010173

  View details for PubMedID 38201600

• Analysis of the Measured FDG Uptake from the First-in-Human Clinical Trial of Biology-Guided Radiotherapy. International journal of radiation oncology, biology, physics Surucu, M., Vitzthum, L., Chang, D. T., Gensheimer, M. F., Kovalchuk, N., Han, B., Iagaru, A. H., Da Silva, A., Narayanan, M., Aksoy, D., Feghali, K., Shirvani, S. M., Maniyedath, A., Cai, B., Pompos, A., Dan, T., Oz, O. K., Iyengar, P., Timmerman, R. D., Garant, A. 2023; 117 (2S): e61-e62

  Abstract

  PURPOSE/OBJECTIVE(S): The RefleXion X1 system is a novel linear accelerator equipped with dual 90° PET arcs incorporated into its architecture to capture emissions from tumors and designed to respond by directing the radiation beam towards target. This study reports on the measured FDG uptake from the first in human multi-institutional clinical trial (BIOGUIDE-X) evaluating the performance and safety of the RefleXion X1 PET-LINAC.MATERIALS/METHODS: A total of nine patients treated with stereotactic body radiotherapy (SBRT) for lung (5) and bone (4) tumors were enrolled in the Cohort II of this study after screening their pre-study diagnostic PET/CT, acquired up to 60 days prior to enrollment, to ensure their tumor size between 2 to 5 cm and SUVmax >6. After CT simulation, the tumor and OARs were delineated, and patients had a 4-pass Imaging-only (BgRT Modeling) PET/CT acquisition on the X1 system to generate biology-guided radiotherapy (BgRT) plans. Before the patients' first and last SBRT fractions, they were injected with FDG, and short PET pre-scan (1-pass) was performed on the X1 followed by a long-PET acquisition (4-pass) to emulate the expected BgRT dose distribution without firing beam. Patients were also imaged on a third-party diagnostic PET/CT scanner after the last-fraction X1 scan. This study compares the SUVmax from the screening PET/CT, X1 Imaging-only scan, X1 PET pre-scan and long scan before the first and last-fractions, and final diagnostic PET/CT.RESULTS: The median time from injection to PET imaging was 84 ± 15.4 mins for X1 Imaging-only (used for generating BgRT plans), 77 ± 21.6 mins for X1 pre-scan (safety check before treatment start), 108+/- 22 mins for X1 long-PET (used to emulate treatment delivery), and 161 ± 23 mins for final diagnostic PET. For a nominal 10 mCi injection, the mean SUVmax for screening imaging performed on the diagnostic PET/CT was 10.8 ± 4.3. For a 15 mCi nominal injection, the mean SUVmax calculated on the X1 was 5.3 ± 2.6, 5.4 ± 2.0, 5.5 ± 2.6, 5.2 ± 1.8 and 5.4 ± 2.2 for the Imaging-only, first-fraction PET pre-scan, first-fraction long PET scan, last-fraction PET pre-scan, and last-fraction long PET scan, respectively. The overall median SUVmax for all patients across all timepoints and scans with X1 was calculated to be 4.8 with a range of 2.4 to 9.8. The median SUVmax for the diagnostic PET/CT scan after the last fraction X1 scan was 15.8 with a range of 8.5 to 27.7.CONCLUSION: The dual PET arcs and limited axial extent of the X1 PET subsystem results in lower system sensitivity in comparison to diagnostic PET scanners equipped with full ring and larger axial extent, as expected. With the same FDG injection, the RefleXion X1 produced SUVmax values that were 30.4 % of the diagnostic PET/CT scanners' values. Nevertheless, the X1 collected sufficient emission data to enable successful completion of emulated BgRT deliveries that met dose accuracy criteria in a clinical setting.

  View details for DOI 10.1016/j.ijrobp.2023.06.782

  View details for PubMedID 37785835

• European Association of Nuclear Medicine Focus 5: Consensus on Molecular Imaging and Theranostics in Prostate Cancer. European urology Oprea-Lager, D. E., MacLennan, S., Bjartell, A., Briganti, A., Burger, I. A., de Jong, I., De Santis, M., Eberlein, U., Emmett, L., Fizazi, K., Gillessen, S., Herrmann, K., Heskamp, S., Iagaru, A., Jereczek-Fossa, B. A., Kunikowska, J., Lam, M., Nanni, C., O'Sullivan, J. M., Panebianco, V., Sala, E., Sathekge, M., Sosnowski, R., Tilki, D., Tombal, B., Treglia, G., Tunariu, N., Walz, J., Yakar, D., Dierckx, R., Sartor, O., Fanti, S. 2023

  Abstract

  In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications.We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa.The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting.Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores.After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [177Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [223Ra]RaCl2 remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both [18F]FDG and PSMA PET prior to [177Lu]Lu-PSMA therapy.There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community.There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide.

  View details for DOI 10.1016/j.eururo.2023.09.003

  View details for PubMedID 37743194

• Reply to Perera Molligoda Arachchige AS [1] CLINICAL AND TRANSLATIONAL IMAGING Laudicella, R., Davidzon, G. A., Dimos, N., Provenzano, G., Iagaru, A., Bisdas, S. 2023

  View details for DOI 10.1007/s40336-023-00597

  View details for Web of Science ID 001067805000001

• Final Analysis of a Prospective, Single-center, Phase II/III Imaging Trial of<SUP>68</SUP>Ga-RM2 PET/MRI in Patients with Biochemical Recurrence of Prostate Cancer Duan, H., Moradi, F., Davidzon, G. A., Liang, T., Song, H., Loening, A., Vasanawala, S., Srinivas, S., Brooks, J. D., Hancock, S. L., Iagaru, A. SPRINGER. 2023: S229

  View details for Web of Science ID 001084059701047

• Modified PROMISE Criteria for Standardized Interpretation of Gastrin Releasing Peptide Receptor (GRPR)-targeted PET Duan, H., Davidzon, G. A., Moradi, F., Liang, T., Song, H., Iagaru, A. SPRINGER. 2023: S542

  View details for Web of Science ID 001084059702325

• International EANM-SNMMI-ISMRM consensus recommendation for PET/MRI in oncology. European journal of nuclear medicine and molecular imaging Veit-Haibach, P., Ahlström, H., Boellaard, R., Delgado Bolton, R. C., Hesse, S., Hope, T., Huellner, M. W., Iagaru, A., Johnson, G. B., Kjaer, A., Law, I., Metser, U., Quick, H. H., Sattler, B., Umutlu, L., Zaharchuk, G., Herrmann, K. 2023

  Abstract

  The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The merged International Society for Magnetic Resonance in Medicine (ISMRM) is an international, nonprofit, scientific association whose purpose is to promote communication, research, development, and applications in the field of magnetic resonance in medicine and biology and other related topics and to develop and provide channels and facilities for continuing education in the field.The ISMRM was founded in 1994 through the merger of the Society of Magnetic Resonance in Medicine and the Society of Magnetic Resonance Imaging. SNMMI, ISMRM, and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine and/or magnetic resonance imaging. The SNMMI, ISMRM, and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and/or magnetic resonance imaging and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each practice guideline, representing a policy statement by the SNMMI/EANM/ISMRM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI, ISMRM, and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging and magnetic resonance imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized. These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNMMI, the ISMRM, and the EANM caution against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

  View details for DOI 10.1007/s00259-023-06406-x

  View details for PubMedID 37624384

  View details for PubMedCentralID 7396397

• International EANM-SNMMI-ISMRM consensus recommendation for PET/MRI in oncology EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Veit-Haibach, P., Ahlstrom, H., Boellaard, R., Delgado Bolton, R. C., Hesse, S., Hope, T., Huellner, M. W., Iagaru, A., Johnson, G. B., Kjaer, A., Law, I., Metser, U., Quick, H. H., Sattler, B., Umutlu, L., Zaharchuk, G., Herrmann, K. 2023

  View details for DOI 10.1007/s00259-023-06406

  View details for Web of Science ID 001059909000001

• PSMA PET for Detection of Recurrence. Seminars in nuclear medicine Duan, H., Iagaru, A. 2023

  Abstract

  Prostate cancer (PC) is a significant health concern worldwide, with high incidence and mortality rates. Early and accurate detection and localization of recurrent disease at biochemical recurrence (BCR) is critical for guiding subsequent therapeutic decisions and improving patient outcomes. At BCR, conventional imaging consisting of CT, MRI, and bone scintigraphy are recommended by US and European guidelines, however, these modalities all bear certain limitations in detecting metastatic disease, particularly in low-volume relapse at low prostate-specific antigen (PSA) levels. Molecular imaging with PET/CT or PET/MRI using prostate-specific membrane antigen (PSMA) targeting radiopharmaceuticals has revolutionized imaging of PC. Particularly at BCR PC, PSMA PET has shown better diagnostic performance compared to conventional imaging in detecting local relapse and metastases, even at very low PSA levels. The most recent version of the National Comprehensive Cancer Network (NCCN) guideline has included PSMA-targeted PET/CT or PET/MRI for the localization of BCR PC. There are several different PSMA-targeting radiopharmaceuticals labeled with different radioisotopes, each with slightly different characteristics, but overall similar high sensitivity and specificity for PC. PSMA-targeted PET has the potential to significantly impact patient care by guiding personalized treatment decisions and thus improving outcomes in BCR PC patients.

  View details for DOI 10.1053/j.semnuclmed.2023.07.002

  View details for PubMedID 37567795

• Modified PROMISE criteria for standardized interpretation of gastrin-releasing peptide receptor (GRPR)-targeted PET. European journal of nuclear medicine and molecular imaging Duan, H., Davidzon, G. A., Moradi, F., Liang, T., Song, H., Iagaru, A. 2023

  Abstract

  There are image interpretation criteria to standardize reporting prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET). As up to 10% of prostate cancer (PC) do not express PSMA, other targets such as gastrin-releasing peptide receptor (GRPR) are evaluated. Research on GRPR-targeted imaging has been slowly increasing in usage at staging and biochemical recurrence (BCR) of PC. We therefore propose a modification of the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria (mPROMISE) for GRPR-targeted PET.[68 Ga]Ga-RM2 PET data from initially prospective studies performed at our institution were retrospectively reviewed: 44 patients were imaged for staging and 100 patients for BCR PC. Two nuclear medicine physicians independently evaluated PET according to the mPROMISE criteria. A third expert reader served as standard reference. Interreader reliability was computed for GRPR expression, prostate bed (T), lymph node (N), skeleton (Mb), organ (Mc) metastases, and final judgment of the scan.The interrater reliability for GRPR PET at staging was moderate for GRPR expression (0.59; 95% confidence interval [CI] 0.40, 0.78), substantial for T-stage (0.78; 95% CI 0.63, 0.94), and almost perfect for N-stage (0.97; 95% CI 0.92, 1.00) and final judgment (0.92; 95% CI 0.82, 1.00). The interreader agreement at BCR showed substantial agreement for GRPR expression (0.70; 95% CI 0.59, 0.81) and final judgment (0.65; 95% CI 0.53, 0.78), while almost perfect agreement was seen across the major categories (T, N, Mb, Mc). Acceptable performance of the mPROMISE criteria was found for all subsets when compared to the standard reference.Interpreting GRPR-targeted PET using the mPROMISE criteria showed its reliability with substantial or almost perfect interrater agreement across all major categories. The proposed modification of the PROMISE criteria will aid clinicians in decreasing the level of uncertainty, and clinical trials to achieve uniform evaluation, reporting, and comparability of GRPR-targeted PET.Clinicaltrials.gov Identifier: NCT03113617 and NCT02624518.

  View details for DOI 10.1007/s00259-023-06385-z

  View details for PubMedID 37555901

  View details for PubMedCentralID 9635676

• A Case-Based Primer on FDG PET/CT for Imaging Cardiovascular Infections: Protocol, Interpretation, and Pitfalls. Zhou, W., Moradi, F., Davidzon, G., Song, H., Grady, E., Nguyen, J., Franc, B., Aparici, C., Iagaru, A., Shah, J. SOC NUCLEAR MEDICINE INC. 2023

  View details for Web of Science ID 001109210201036

• Assessment of the response of treatment with 18F-DCFPYL PET/CT in patients with prostate cancer Na, S., Duan, H., Song, H., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2023

  View details for Web of Science ID 001109210201125

• Total and Anatomically Contextualized Quantitative 18F-DCFPyL PET at biochemical recurrence predicts subsequent biochemical progression free survival in prostate cancer patients Song, H., Duan, H., Ferri, V., Na, S., Davidzon, G., Franc, B., Aparici, C., Moradi, F., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2023

  View details for Web of Science ID 001109210201271

• Final Analysis of a Prospective, Single-center, Phase II/III Imaging Trial of 68Ga-RM2 PET/MRI in Patients with Biochemical Recurrence of Prostate Cancer Duan, H., Moradi, F., Davidzon, G., Liang, T., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2023

  View details for Web of Science ID 001109210201177

• Modified PROMISE Criteria for Standardized Interpretation of Gastrin Releasing Peptide Receptor (GRPR)-targeted PET Duan, H., Davidzon, G., Moradi, F., Liang, T., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2023

  View details for Web of Science ID 001109210201173

• Total and anatomically contextualized quantitative 18F-DCFPyL PET at biochemical recurrence to predict subsequent biochemical progression free survival in patients with prostate cancer Song, H., Sjostrand, K., Duan, H., Ferri, V., Aparici, C., Davidzon, G., Franc, B., Moradi, F., Anand, A., Iagaru, A. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772002474

• Rapid dynamic reconstruction using list mode data for monitoring PET image quality accurately predicts final image noise and perceived quality Moradi, F., Khalighi, M., Su, K., Zhang, X., Wollenweber, S., Spangler-Bickell, M., Bharathi, P., Franc, B., Davidzon, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2023

  View details for Web of Science ID 001109210200126

• ChatGPT in nuclear medicine and radiology: lights and shadows in the AI bionetwork CLINICAL AND TRANSLATIONAL IMAGING Laudicella, R., Davidzon, G. A., Dimos, N., Provenzano, G., Iagaru, A., Bisdas, S. 2023

  View details for DOI 10.1007/s40336-023-00574-4

  View details for Web of Science ID 000995015300001

• 2022 SNMMI Highlights Lecture: General Nuclear Medicine. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Iagaru, A. 2023

  Abstract

  The Highlights Lectures at the closing sessions of SNMMI Annual Meetings were originated and presented for more than 30 y by Henry N. Wagner, Jr., MD. Beginning in 2010, the duties of summarizing selected significant presentations at the meeting were divided annually among 4 distinguished nuclear and molecular medicine subject matter experts. The 2022 Highlights Lectures were delivered on June 14 at the SNMMI Annual Meeting in Vancouver, Canada. This month we feature the lecture by Andrei Iagaru, MD, Professor of Radiology-Nuclear Medicine at Stanford University School of Medicine (CA) and Chief of the Division of Nuclear Medicine and Molecular Imaging at Stanford HealthCare, who spoke on general nuclear medicine highlights from the meeting. Note that in the following presentation summary, numerals in brackets represent abstract numbers as published in The Journal of Nuclear Medicine (2022;63[suppl 2]).

  View details for DOI 10.2967/jnumed.123.265758

  View details for PubMedID 37055218

• SPECT at the speed of PET: a feasibility study of CZT-based whole-body SPECT/CT in the post 177Lu-DOTATATE and 177Lu-PSMA617 setting. European journal of nuclear medicine and molecular imaging Song, H., Ferri, V., Duan, H., Aparici, C. M., Davidzon, G., Franc, B. L., Moradi, F., Nguyen, J., Shah, J., Iagaru, A. 2023

  Abstract

  To evaluate the feasibility of using the StarGuide (General Electric Healthcare, Haifa, Israel), a new generation multi-detector cadmium-zinc-telluride (CZT)-based SPECT/CT, for whole-body imaging in the setting of post-therapy imaging of 177Lu-labeled radiopharmaceuticals.Thirty-one patients (34-89 years old; mean ± SD, 65.5 ± 12.1) who were treated with either 177Lu-DOTATATE (n=17) or 177Lu-PSMA617 (n=14) as part of standard of care were scanned post-therapy with the StarGuide; some were also scanned with the standard GE Discovery 670 Pro SPECT/CT. All patients had either 64Cu-DOTATATE or 18F-DCFPyL PET/CT prior to first cycle of therapy for eligibility check. The detection/targeting rate (lesion uptake greater than blood pool uptake) of large lesions meeting RECIST 1.1 size criteria on post-therapy StarGuide SPECT/CT was evaluated and compared to the standard design GE Discovery 670 Pro SPECT/CT (when available) and pre-therapy PET by two nuclear medicine physicians with consensus read.This retrospective analysis identified a total of 50 post-therapy scans performed with the new imaging protocol from November 2021 to August 2022. The StarGuide system acquired vertex to mid-thighs post-therapy SPECT/CT scans with 4 bed positions, 3 min/bed and a total scan time of 12 min. In comparison, the standard GE Discovery 670 Pro SPECT/CT system typically acquires images in 2 bed positions covering the chest, abdomen, and pelvis with a total scan time of 32 min. The pre-therapy 64Cu-DOTATATE PET takes 20 min with 4 bed positions on GE Discovery MI PET/CT, and 18F-DCFPyL PET takes 8-10 min with 4-5 bed positions on GE Discovery MI PET/CT. This preliminary evaluation showed that the post-therapy scans acquired with faster scanning time using StarGuide system had comparable detection/targeting rate compared to the Discovery 670 Pro SPECT/CT system and detected large lesions defined by RECIST criteria on the pre-therapy PET scans.Fast acquisition of whole-body post-therapy SPECT/CT is feasible with the new StarGuide system. Short scanning time improves the patients' clinical experience and compliance which may lead to increased adoption of post-therapy SPECT. This opens the possibility to offer imaged-based treatment response assessment and personalized dosimetry to patients referred for targeted radionuclide therapies.

  View details for DOI 10.1007/s00259-023-06176-6

  View details for PubMedID 36869177

  View details for PubMedCentralID 6667427

• <SUP>89</SUP>Zr-DFO-girentuximab for PET imaging of solid tumors likely to express high levels of carbonic anhydrase IX. Iagaru, A., Takalkar, A., Higgins, G., Kiser, J., Tauchmanova, L., Shah, S., Vadali, K., Hayward, C., Crowley, J. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001098050200078

• Neuroendocrine Tumor Diagnosis: PET/MR Imaging. PET clinics Duan, H., Iagaru, A. 2023

  Abstract

  Imaging plays a critical role in the diagnosis and management of neuroendocrine tumors (NETs). The initial workup of the primary tumor, including its characterization, local and distant staging, defines subsequent treatment decisions. Functional imaging using hybrid systems, such as PET combined with computed tomography, has become the gold standard. As NETs majorly arise from the gastrointestinal system and metastasize primarily to the liver, simultaneous PET and MR imaging with its high soft tissue contrast might be a valuable clinical one-stop-shop whole-body imaging tool. This review presents the current status and challenges of PET/MR imaging for diagnosis of NETs.

  View details for DOI 10.1016/j.cpet.2022.11.008

  View details for PubMedID 36707370

• Overview and Recent Advances in 18F-FDG PET/CT for Evaluation of Pediatric Lymphoma Seminars in Nuclear Medicine Guja, K. E., Nadel, H., Iagaru, A. 2023; 53 (3): 400-412

  View details for DOI 10.1053/j.semnuclmed.2022.10.001

• A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Duan, H., Ghanouni, P., Daniel, B., Rosenberg, J., Thong, A., Kunder, C., Mari Aparici, C., Davidzon, G. A., Moradi, F., Sonn, G. A., Iagaru, A. 2022

  Abstract

  Purpose: Targeting of lesions seen on multiparametric MRI (mpMRI) improves prostate cancer (PC) detection at biopsy. However, 20-65% of highly suspicious lesions on mpMRI (PI-RADS 4 or 5) are false positives (FP), while 5-10% of clinically significant PC (csPC) are missed. Prostate specific membrane antigen (PSMA) and gastrin-releasing peptide receptors (GRPR) are both overexpressed in PC. We therefore aimed to evaluate the potential of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for biopsy guidance in patients with suspected PC. Methods: A highly selective cohort of 13 men, aged 58.0±7.1 years, with suspected PC (persistently high prostate-specific antigen [PSA] and PSA density) but negative or equivocal mpMRI and/or negative biopsy were prospectively enrolled to undergo 68Ga-PSMA11 and 68Ga-RM2 PET/MRI. PET/MRI included whole-body and dedicated pelvic imaging after a delay of 20 minutes. All patients had targeted biopsy of any lesions seen on PET followed by standard 12-core biopsy. Maximum standardized uptake values (SUVmax) of suspected PC lesions were collected and compared to gold standard biopsy. Results: PSA and PSA density at enrollment were 9.8±6.0 (1.5-25.5) ng/mL and 0.20±0.18 (0.06-0.68) ng/mL2, respectively. Standardized systematic biopsy revealed a total of 14 PC in 8 participants: 7 were csPC and 7 were non-clinically significant PC (ncsPC). 68Ga-PSMA11 identified 25 lesions, of which 11 (44%) were true positive (TP) (5 csPC). 68Ga-RM2 showed 27 lesions, of which 14 (52%) were TP, identifying all 7 csPC and also 7 ncsPC. There were 17 concordant lesions in 11 patients vs. 14 discordant lesions in 7 patients between 68Ga-PSMA11 and 68Ga-RM2 PET. Incongruent lesions had the highest rate of FP (12 FP vs. 2 TP). SUVmax was significantly higher for TP than FP lesions in delayed pelvic imaging for 68Ga-PSMA11 (6.49±4.14 vs. 4.05±1.55, P = 0.023) but not for whole-body images, nor for 68Ga-RM2. Conclusion: Our results show that 68Ga-PSMA11 and 68Ga-RM2 PET/MRI are feasible for biopsy guidance in suspected PC. Both radiopharmaceuticals detected additional clinically significant cancers not seen on mpMRI in this selective cohort. 68Ga-RM2 PET/MRI identified all csPC confirmed at biopsy.

  View details for DOI 10.2967/jnumed.122.264448

  View details for PubMedID 36396456

• A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Evaluation of Prostate Cancer Response to High Intensity Focused Ultrasound (HIFU) Therapy. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Duan, H., Ghanouni, P., Daniel, B., Rosenberg, J., Davidzon, G. A., Mari Aparici, C., Kunder, C., Sonn, G., Iagaru, A. 2022

  Abstract

  Rationale: Focal therapy for localized prostate cancer (PC) using high intensity focused ultrasound (HIFU) is gaining in popularity as it is non-invasive and associated with fewer side effects than standard whole-gland treatments. However, better methods to evaluate response to HIFU ablation are an unmet need. Prostate specific membrane antigen (PSMA) and gastrin-releasing peptide receptors (GRPR) are both overexpressed in PC. In this study, we evaluated a novel approach of using both 68Ga-RM2 and 68Ga-PSMA11 PET/MRI in each patient before and after HIFU to assess accuracy of target tumor localization and response to treatment. Methods: Fourteen men, 64.5 ± 8.0 (range 48-78) years-old, with newly diagnosed PC were prospectively enrolled. Pre-HIFU, patients underwent prostate biopsy, multiparametric MRI (mpMRI), 68Ga-PSMA11, and 68Ga-RM2 PET/MRI. Response to treatment was assessed at a minimum of 6 months after HIFU with prostate biopsy (n = 13), as well as 68Ga-PSMA11 and 68Ga-RM2 PET/MRI (n = 14). Maximum and peak standardized uptake values (SUVmax and SUVpeak) of known or suspected PC lesions were collected. Results: Pre-HIFU biopsy revealed 18 cancers of which 14 were clinically significant (Gleason score ≥3+4). mpMRI identified 18 lesions; 14 of them were ≥PI-RADS 4. 68Ga-PSMA11 and 68Ga-RM2 PET/MRI each showed 23 positive intraprostatic lesions; 21 were congruent in 13 patients and five were incongruent in 5 patients. Pre-HIFU, 68Ga-PSMA11 identified all target tumors while 68Ga-RM2 PET/MRI missed two tumors. Post-HIFU, 68Ga-RM2 and 68Ga-PSMA11 PET/MRI both identified clinically significant residual disease in one patient. Three significant ipsilateral recurrent lesions were identified, whereas one was missed by 68Ga-PSMA11. Pre-treatment prostate specific antigen (PSA) decreased significantly after HIFU by 66%. Concordantly, pre-treatment SUVmax decreased significantly after HIFU for 68Ga-PSMA11 (P = 0.001) and 68Ga-RM2 (P = 0.005). Conclusion: The results of this pilot study show that 68Ga-PSMA11 and 68Ga-RM2 PET/MRI identified the target tumor for HIFU in 100% and 86%, respectively, and accurately verified response to treatment. PET might be a useful tool in the guidance and monitoring of treatment success in patients receiving focal therapy for PC. These preliminary findings warrant larger studies for validation.

  View details for DOI 10.2967/jnumed.122.264783

  View details for PubMedID 36328488

• Image-mode performance characterization of a positron emission tomography subsystem designed for Biology-guided radiotherapy (BgRT). The British journal of radiology Hu, Z., Bieniosek, M., Ferri, V., Iagaru, A., Kovalchuk, N., Han, B., Xing, L., Vitzthum, L., Olcott, P., Narayanan, M., Laurence, T., Ren, Y., Oderinde, O. M., Shirvani, S. M., Chang, D., Surucu, M. 2022: 20220387

  Abstract

  OBJECTIVES: In this study, we characterize the imaging-mode performance of the positron emission tomography (PET) subsystem of the RefleXion X1 machine using the NEMA NU-2 2018 standard.METHODS: The X1 machine consists of two symmetrically opposing 900 arcs of PET detectors incorporated into the architecture of a ring-gantry linear accelerator rotating up to 60RPM. PET emissions from a tumor are detected by the PET detectors and used to guide the delivery of radiation beam. Imaging performance of the PET subsystem on X1 machine was evaluated based on1 sensitivity of the PET detectors,2 spatial resolution,3 count-loss performance,4 Image quality, and daily system performance check.RESULTS: PET subsystem sensitivity was measured as 0.183 and 0.161 cps/kBq at the center and off-center positions, respectively. Spatial resolution: average FWHM values of 4.3, 5.1, and 6.7mm for the point sources at 1, 10, and 20cm off center, respectively were recorded. For count loss, max NECR: 2.63 kcps, max true coincidence rate: 5.56 kcps, and scatter fraction: 39.8%. The 10mm sphere was not visible. Image-quality contrast values were: 29.6%, 64.9%, 66.5%, 81.8%, 81.2%, and background variability: 14.8%, 12.4%, 10.3%, 8.8%, 8.3%, for the 13, 17, 22, 28, 37mm sphere sizes, respectively.CONCLUSIONS: When operating in an imaging mode, the spatial resolution and image contrast of the X1 PET subsystem were comparable to those of typical diagnostic imaging systems for large spheres, while the sensitivity and count rate were lower due to the significantly smaller PET detector area in the X1 system. Clinical efficacy when used in BgRT remains to be validated.ADVANCES IN KNOWLEDGE: This is the first performance evaluation of the PET subsystem on the novel BgRT machine. The dual arcs rotating PET subsystem on RefleXion X1 machine performance is comparable to those of the typical diagnostic PET system based on the spatial resolution and image contrast for larger spheres.

  View details for DOI 10.1259/bjr.20220387

  View details for PubMedID 36317922

• PET Imaging Using Gallium-68 (68Ga) RM2. PET clinics Duan, H., Iagaru, A. 2022

  Abstract

  Molecular imaging is advancing rapidly with promising new molecular targets emerging for theragnostic, ie, imaging and treatment with the same compound, to provide targeted, personalized medicine. Gastrin-releasing peptide receptors (GRPR) are overexpressed in prostate cancer. Gallium-68 (68Ga) RM2 is a GRPR antagonist and shows high sensitivity and specificity for the detection of primary prostate cancer and recurrent disease. However, compared with the widely used 68Ga-PSMA11 and 18F-DCFPyL, a discordance in uptake pattern is seen reflecting the heterogeneity in tumor biology of prostate cancer. In this review, we present the background, current status, and future perspectives of PET imaging using 68Ga-RM2.

  View details for DOI 10.1016/j.cpet.2022.07.006

  View details for PubMedID 36153233

• The use of advanced imaging in guiding the further investigation and treatment of primary prostate cancer CANCER IMAGING Duan, H., Iagaru, A. 2022; 22 (1): 45

  Abstract

  In the era of precision medicine, oncological imaging techniques are advancing at a rapid pace, particularly molecular imaging with promising new targets for prostate cancer (PC) such as gastrin releasing peptide receptors (GRPR) along the established and indispensable prostate specific membrane antigen (PSMA). As PC is characterized by heterogenous tumor biology ranging from indolent to aggressive disease, distinguishing clinically significant tumors from indolent disease is critical. Multiparametric MRI- and PET-targeted prostate biopsies mitigate the shortcomings and risks of standard systematic template biopsy by identifying more significant cancers.Focal treatment for localized disease is a minimally invasive approach that targets the index tumor - the lesion of the highest grade - while sparing the surrounding healthy tissue. Real-time MRI-guidance and thermal control with MR-thermometry, improves treatment accuracy and results in lower rates of functional side effects. PET imaging could be an useful tool to assess response to treatment compared to invasive prostate biopsies.In this comprehensive review, we focus on the image-guided detection and treatment of localized primary prostate cancer, its current status and future perspectives.

  View details for DOI 10.1186/s40644-022-00481-3

  View details for Web of Science ID 000849470600002

  View details for PubMedID 36057766

• Novel CZT-based multi detector SPECT/CT system: daily QCs and performance evaluation at one year after installation Ferri, V., Luong, K., Castaneda, P., Iagaru, A. SPRINGER. 2022: S340

  View details for Web of Science ID 000857046601101

• Head-to-head Comparison of a Conventional or CZT-based SPECT/CT with a Next Generation Multidetector CZT-based SPECT/CT System Duan, H., Ferri, V., Castaneda, P., Visser, T., Luong, K., Davidzon, G. A., Aparici, C., Iagaru, A. SPRINGER. 2022: S263

  View details for Web of Science ID 000857046600550

• TOF image enhancement of non-TOF PET scans using deep learning: a generalizability study Mehranian, A., Wollenweber, S. D., Bradley, K. M., Walker, M. D., Huellner, M., Guerra, L., Landoni, C., Iagaru, A., Khalighi, M., Kotasidis, F., Su, K., Johnsen, R., McGowan, D. R. SPRINGER. 2022: S618

  View details for Web of Science ID 000857046603040

• Modified PROMISE Criteria for Standardized Interpretation of GRPR-targeted PET Duan, H., Davidzon, G. A., Moradi, F., Liang, T., Iagaru, A. SPRINGER. 2022: S288

  View details for Web of Science ID 000857046600603

• A Pilot Study of Ga-68-PSMA11 and 68Ga-RM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer Duan, H., Ghanouni, P., Daniel, B., Rosenberg, J., Thong, A., Sonn, G. A., Kunder, C., Davidzon, G. A., Aparici, C., Moradi, F., Iagaru, A. SPRINGER. 2022: S484

  View details for Web of Science ID 000857046602091

• A Pilot Study of Ga-68-PSMA11 and Ga-68-RM2 PET/MRI for Evaluation of Prostate Cancer Response to High Intensity Focused Ultrasound (HIFU) Therapy Duan, H., Ghanouni, P., Daniel, B., Rosenberg, J., Davidzon, G. A., Aparici, C., Thong, A., Sonn, G. A., Kunder, C., Iagaru, A. SPRINGER. 2022: S497-S498

  View details for Web of Science ID 000857046602123

• 89Zr-panitumumab combined with 18F-FDG-PET improves detection and staging of head and neck squamous cell carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research Lee, Y., van den Berg, N. S., Duan, H., Azevedo, E. C., Ferri, V., Hom, M., Raymundo, R. C., Valencia, A., Castillo, J., Shen, B., Zhou, Q., Freeman, L., Koran, M. E., Kaplan, M. J., Colevas, A. D., Baik, F. M., Chin, F. T., Martin, B. A., Iagaru, A., Rosenthal, E. L. 2022

  Abstract

  PURPOSE: Determine the safety and specificity of a tumor-targeted radiotracer (89Zr-pan) in combination with 18F-FDG PET/CT to improve diagnostic accuracy in head and neck squamous cell carcinoma (HNSCC).EXPERIMENTAL DESIGN: Adult patients with biopsy-proven HNSCC scheduled for standard of care surgery were enrolled in a clinical trial and underwent systemic administration of 89Zirconium-panitumumab and panitumumab-IRDye800 followed by preoperative 89Zr-pan PET/CT and intraoperative fluorescence imaging. The sensitivity, specificity, and AUC were evaluated.RESULTS: A total of fourteen patients were enrolled and completed the study. Four patients (28.5%) had areas of high 18F-FDG uptake outside the head and neck region with maximum standardized uptake values (SUVmax) greater than 2.0 that were not detected on 89Zr-pan PET/CT. These four patients with incidental findings underwent further workup and had no evidence of cancer on biopsy or clinical follow-up. Forty-eight lesions (primary tumor, LNs, incidental findings) with SUVmax ranging 2.0 - 23.6 were visualized on 18F-FDG PET/CT; 34 lesions on 89Zr-pan PET/CT with SUVmax ranging 0.9 - 10.5. The combined ability of 18F-FDG PET/CT and 89Zr-pan PET/CT to detect HNSCC in the whole body was improved with higher specificity of 96.3% (confidence interval (CI) 89.2 - 100%) compared to 18F-FDG PET/CT alone with specificity of 74.1% (CI 74.1 - 90.6%). One possibly related grade 1 adverse event of prolonged QTc (460 ms) was reported but resolved in follow-up.CONCLUSIONS: 89Zr-pan PET/CT imaging is safe and may be valuable in discriminating incidental findings identified on 18F-FDG-PET/CT from true positive lesions and in localizing metastatic LNs.

  View details for DOI 10.1158/1078-0432.CCR-22-0094

  View details for PubMedID 35929985

• Randomized phase II study of platinum and etoposide (EP) versus temozolomide and capecitabine (CAPTEM) in patients (pts) with advanced G3 non-small cell gastroenteropancreatic neuroendocrine neoplasms (GEPNENs): ECOG-ACRIN EA2142. Eads, J., Catalano, P. J., Fisher, G. A., Rubin, D., Iagaru, A., Klimstra, D. S., Konda, B., Kwong, M. S., Chan, J. A., De Jesus-Acosta, A., Halfdanarson, T., Shaib, W., Soares, H. P., Hong, S., Wong, T. Z., O'Dwyer, P. J. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680301186

• PSMA theragnostics for metastatic castration resistant prostate cancer. Translational oncology Song, H., Guja, K. E., Iagaru, A. 2022; 22: 101438

  Abstract

  There has been tremendous growth in the development of theragnostics for personalized cancer diagnosis and treatment over the past two decades. In prostate cancer, the new generation of prostate specific membrane antigen (PSMA) small molecular inhibitor-based imaging agents achieve extraordinary tumor to background ratios and allow their therapeutic counterparts to deliver effective tumor doses while minimizing normal tissue toxicity. The PSMA targeted small molecule positron emission tomography (PET) agents 18F-DCFPyL (2-(3-{1-carboxy-5-((6-(18)F-fluoro-pyridine-3-carbonyl)-amino)-pentyl}-ureido)-pentanedioic acid) and Gallium-68 (68Ga)-PSMA-11 have been approved by the United States Food and Drug Administration (FDA) for newly diagnosed high risk prostate cancer patients and for patients with biochemical recurrence. More recently, the Phase III VISION trial showed that Lutetium-177 (177Lu)-PSMA-617 treatment increases progression-free survival and overall survival in patients with heavily pre-treated advanced PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). Here, we review the PSMA targeted theragnostic pairs under clinical investigation for detection and treatment of metastatic prostate cancer.

  View details for DOI 10.1016/j.tranon.2022.101438

  View details for PubMedID 35659674

• Correlation of 68Ga-RM2 PET with Post-Surgery Histopathology Findings in Patients with Newly Diagnosed Intermediate- or High-Risk Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Duan, H., Baratto, L., Fan, R. E., Soerensen, S. J., Liang, T., Chung, B. I., Thong, A. E., Gill, H., Kunder, C., Stoyanova, T., Rusu, M., Loening, A. M., Ghanouni, P., Davidzon, G. A., Moradi, F., Sonn, G. A., Iagaru, A. 2022

  Abstract

  Rationale: 68Ga-RM2 targets gastrin-releasing peptide receptors (GRPR), which are overexpressed in prostate cancer (PC). Here, we compared pre-operative 68Ga-RM2 PET to post-surgery histopathology in patients with newly diagnosed intermediate- or high-risk PC. Methods: Forty-one men, 64.0+/-6.7-year-old, were prospectively enrolled. PET images were acquired 42 - 72 (median+/-SD 52.5+/-6.5) minutes after injection of 118.4 - 247.9 (median+/-SD 138.0+/-22.2)MBq of 68Ga-RM2. PET findings were compared to pre-operative mpMRI (n = 36) and 68Ga-PSMA11 PET (n = 17) and correlated to post-prostatectomy whole-mount histopathology (n = 32) and time to biochemical recurrence. Nine participants decided to undergo radiation therapy after study enrollment. Results: All participants had intermediate (n = 17) or high-risk (n = 24) PC and were scheduled for prostatectomy. Prostate specific antigen (PSA) was 8.8+/-77.4 (range 2.5 - 504) ng/mL, and 7.6+/-5.3 (range 2.5 - 28.0) ng/mL when excluding participants who ultimately underwent radiation treatment. Pre-operative 68Ga-RM2 PET identified 70 intraprostatic foci of uptake in 40/41 patients. Post-prostatectomy histopathology was available in 32 patients in which 68Ga-RM2 PET identified 50/54 intraprostatic lesions (detection rate = 93%). 68Ga-RM2 uptake was recorded in 19 non-enlarged pelvic lymph nodes in 6 patients. Pathology confirmed lymph node metastases in 16 lesions, and follow-up imaging confirmed nodal metastases in 2 lesions. 68Ga-PSMA11 and 68Ga-RM2 PET identified 27 and 26 intraprostatic lesions, respectively, and 5 pelvic lymph nodes each in 17 patients. Concordance between 68Ga-RM2 and 68Ga-PSMA11 PET was found in 18 prostatic lesions in 11 patients, and 4 lymph nodes in 2 patients. Non-congruent findings were observed in 6 patients (intraprostatic lesions in 4 patients and nodal lesions in 2 patients). Both 68Ga-RM2 and 68Ga-PSMA11 had higher sensitivity and accuracy rates with 98%, 89%, and 95%, 89%, respectively, compared to mpMRI at 77% and 77%. Specificity was highest for mpMRI with 75% followed by 68Ga-PSMA11 (67%), and 68Ga-RM2 (65%). Conclusion: 68Ga-RM2 PET accurately detects intermediate- and high-risk primary PC with a detection rate of 93%. In addition, it showed significantly higher specificity and accuracy compared to mpMRI and similar performance to 68Ga-PSMA11 PET. These findings need to be confirmed in larger studies to identify which patients will benefit from one or the other or both radiopharmaceuticals.

  View details for DOI 10.2967/jnumed.122.263971

  View details for PubMedID 35552245

• 68Ga-PSMA-11 PET/MRI in patients with newly diagnosed intermediate or high-risk prostate adenocarcinoma: PET findings correlate with outcomes after definitive treatment. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Moradi, F., Duan, H., Song, H., Davidzon, G. A., Chung, B. I., Thong, A. E., Loening, A. M., Ghanouni, P., Sonn, G., Iagaru, A. 2022

  Abstract

  Prostate-specific membrane antigen (PSMA) PET offers superior accuracy to other imaging modalities in initial staging of prostate cancer and is more likely to affect management. We examined the prognostic value of 68Ga-PSMA-11 uptake in primary lesion and presence of metastatic disease on PET in newly diagnosed prostate cancer patients prior to initial therapy. Methods: In a prospective study from April 2016 to December 2020, 68Ga-PSMA-11 PET/MRI was done in men with new diagnosis of intermediate or high-grade prostate cancer who were candidates for prostatectomy. Patients were followed up after initial therapy for up to 5 years. We examined the Kendall correlation between PET (intense uptake in primary lesion and presence of metastatic disease) and clinical and pathologic findings (grade group, extraprostatic extension, nodal involvement) relevant for risk stratification, and examined the relationship between PET findings and outcome using Kaplan-Meier analysis. Results: Seventy-three men, 64.0±6.3 years of age were imaged. Seventy-two had focal uptake in prostate and in 20 (27%), PSMA-avid metastatic disease was identified. Uptake correlated with grade group and prostate-specific antigen (PSA). Presence of PSMA metastasis correlated with grade group and pathologic nodal stage. PSMA PET had higher per-patients positivity than nodal dissection in patients with only 5-15 nodes removed (8/41 vs. 3/41) but lower positivity if more than 15 nodes were removed (13/21 vs. 10/21). High uptake in primary (SUVmax>12.5, P = .008) and presence of PSMA metastasis (P = .013) were associated with biochemical failure, and corresponding hazard ratios for recurrence within 2-years (4.93 and 3.95, respectively) were similar or higher than other clinicopathologic prognostic factors. Conclusions: 68Ga-PSMA-11 PET can risk stratify patients with intermediate or high-grade prostate cancer prior to prostatectomy based on degree of uptake in prostate and presence of metastatic disease.

  View details for DOI 10.2967/jnumed.122.263897

  View details for PubMedID 35512996

• PSMA and Choline PET for the Assessment of Response to Therapy and Survival Outcomes in Prostate Cancer Patients: A Systematic Review from the Literature. Cancers Alongi, P., Laudicella, R., Lanzafame, H., Farolfi, A., Mapelli, P., Picchio, M., Burger, I. A., Iagaru, A., Minutoli, F., Evangelista, L. 2022; 14 (7)

  Abstract

  The aims of this systematic review were to (1) assess the utility of PSMA-PET and choline-PET in the assessment of response to systemic and local therapy, and to (2) determine the value of both tracers for the prediction of response to therapy and survival outcomes in prostate cancer. We performed a systematic literature search in PubMed/Scopus/Google Scholar/Cochrane/EMBASE databases (between January 2010 and October 2021) accordingly. The quality of the included studies was evaluated following the "Quality Assessment of Prognostic Accuracy Studies" tool (QUAPAS-2). We selected 40 articles: 23 articles discussed the use of PET imaging with [68Ga]PSMA-11 (16 articles/1123 patients) or [11C]/[18F]Choline (7 articles/356 patients) for the prediction of response to radiotherapy (RT) and survival outcomes. Seven articles (three with [68Ga]PSMA-11, three with [11C]Choline, one with [18F]Choline) assessed the role of PET imaging in the evaluation of response to docetaxel (as neoadjuvant therapy in one study, as first-line therapy in five studies, and as a palliative regimen in one study). Seven papers with radiolabeled [18F]Choline PET/CT (n = 121 patients) and three with [68Ga]PSMA-11 PET (n = 87 patients) were selected before and after enzalutamide/abiraterone acetate. Finally, [18F]Choline and [68Ga]PSMA-11 PET/CT as gatekeepers for the treatment of metastatic prostate cancer with Radium-223 were assessed in three papers. In conclusion, in patients undergoing RT, radiolabeled choline and [68Ga]PSMA-11 have an important prognostic role. In the case of systemic therapies, the role of such new-generation imaging techniques is still controversial without sufficient data, thus requiring additional in this scenario.

  View details for DOI 10.3390/cancers14071770

  View details for PubMedID 35406542

• Correction to: Unconventional non-amino acidic PET radiotracers for molecular imaging in gliomas. European journal of nuclear medicine and molecular imaging Laudicella, R., Quartuccio, N., Argiroffi, G., Alongi, P., Baratto, L., Califaretti, E., Frantellizzi, V., De Vincentis, G., Del Sole, A., Evangelista, L., Baldari, S., Bisdas, S., Ceci, F., Iagaru, A., Young Italian Association of Nuclear Medicine (AIMN) group 2022

  View details for DOI 10.1007/s00259-022-05760-6

  View details for PubMedID 35301587

• Evaluation of Liver and Renal Toxicity in Peptide Receptor Radionuclide Therapy for Somatostatin Receptor Expressing Tumors: A 2-Year Follow-Up. The oncologist Duan, H., Ferri, V., Fisher, G. A., Shaheen, S., Davidzon, G. A., Iagaru, A., Mari Aparici, C. 2022

  Abstract

  Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin receptor (SSR) analogs is now an established systemic treatment for neuroendocrine tumors (NET). However, more short- and long-term data about renal and hepatotoxicity is needed. Here we present our experience in this clinical scenario.Eighty-six patients with progressive SSR-expressing malignancies underwent PRRT with Lu-177 Dotatate and were followed up for up to 2 years. Laboratory tests were done 1 week before each cycle and every 2 months at follow-up. Hepatic and renal toxicity was determined based on NCI CTCAE V5.0.55/86 (64%) patients completed all 4 cycles of PRRT; 18/86 (20.9%) are currently being treated; 13/86 (15.1%) had to discontinue PRRT: 4/13 (31%) due to hematologic toxicity, 9/13 (69%) due to non-PRRT-related comorbidities. Out of the patients who finished treatment, only transient grade 2 toxicities were observed during PRRT: hypoalbuminemia in 5.5% (3/55), and renal toxicity (serum creatinine and estimated glomerular filtration rate) in 1.8% (1/55). No grade 3 or 4 liver and renal toxicity occurred. Patients presenting with impaired liver or renal function prior to PRRT, either improved or had stable findings. No deterioration was observed.Peptide receptor radionuclide therapy does not have a negative impact on liver and renal function, even in patients with pre-existing impaired parameters. No grade 3 or 4 hepatic or renal toxicity was identified. Only transient grade 2 hypoalbuminemia in 5.5% and nephrotoxicity in 1.8% of patients were seen during PRRT.

  View details for DOI 10.1093/oncolo/oyab072

  View details for PubMedID 35641196

• Evaluation of Liver and Renal Toxicity in Peptide Receptor Radionuclide Therapy for Somatostatin Receptor Expressing Tumors: A 2-Year Follow-Up ONCOLOGIST Duan, H., Ferri, V., Fisher, G., Shaheen, S., Davidzon, G., Iagaru, A., Aparici, C. 2022

  View details for DOI 10.1093/oncolo/oyab072

  View details for Web of Science ID 000769640100001

• Peptide Receptor Radionuclide Therapy (PRRT) in Advanced Pheochromocytoma and Paraganglioma From a Single Institution Experience Duan, H., Ferri, V., Fisher, G. A., Shaheen, S., Davidzon, G. A., Moradi, F., Nguyen, J., Franc, B. L., Iagaru, A., Aparici, C. LIPPINCOTT WILLIAMS & WILKINS. 2022: E42-E43

  View details for Web of Science ID 000819123700057

• Evaluation of interim Dotatate-PET after two cycles of Peptide Receptor Radionuclide Therapy (PRRT) in neuroendocrine tumors (NET) Duan, H., Song, H., Ferri, Fisher, G., Shaheen, S., Shah, J., Nguyen, J., Moradi, F., Davidzon, G., Franc, B., Iagaru, A., Mari, A. C. WILEY. 2022: 141

  View details for Web of Science ID 000779149500128

• Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN Haddad, R. I., Bischoff, L., Ball, D., Bernet, V., Blomain, E., Busaidy, N. L., Campbell, M., Dickson, P., Duh, Q., Ehya, H., Goldner, W. S., Guo, T., Haymart, M., Holt, S., Hunt, J. P., Iagaru, A., Kandeel, F., Lamonica, D. M., Mandel, S., Markovina, S., McIver, B., Raeburn, C. D., Rezaee, R., Ridge, J. A., Roth, M. Y., Scheri, R. P., Shah, J. P., Sipos, J. A., Sippel, R., Sturgeon, C., Wang, T. N., Wirth, L. J., Wong, R. J., Yeh, M., Cassara, C. J., Darlow, S. 2022; 20 (8): 925-951

  Abstract

  Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hurthle cell carcinoma).

  View details for DOI 10.6004/jnccn.2022.0040

  View details for PubMedID 35948029

• Radiotheranostics - Precision Medicine in Nuclear Medicine and Molecular Imaging. Nanotheranostics Duan, H., Iagaru, A., Aparici, C. M. 1800; 6 (1): 103-117

  Abstract

  'See what you treat and treat what you see, at a molecular level', could be the motto of theranostics. The concept implies diagnosis (imaging) and treatment of cells (usually cancer) using the same molecule, thus guaranteeing a targeted cytotoxic approach of the imaged tumor cells while sparing healthy tissues. As the brilliant late Sam Gambhir would say, the imaging agent acts like a 'molecular spy' and reveals where the tumoral cells are located and the extent of disease burden (diagnosis). For treatment, the same 'molecular spy' docks to the same tumor cells, this time delivering cytotoxic doses of radiation (treatment). This duality represents the concept of a 'theranostic pair', which follows the scope and fundamental principles of targeted precision and personalized medicine. Although the term theranostic was noted in medical literature in the early 2000s, the principle is not at all new to nuclear medicine. The first example of theranostic dates back to 1941 when Dr. Saul Hertz first applied radioiodine for radionuclide treatment of thyroid cells in patients with hyperthyroidism. Ever since, theranostics has been an integral element of nuclear medicine and molecular imaging. The more we understand tumor biology and molecular pathology of carcinogenesis, including specific mutations and receptor expression profiles, the more specific these 'molecular spies' can be developed for diagnostic molecular imaging and subsequent radionuclide targeted therapy (radiotheranostics). The appropriate selection of the diagnostic and therapeutic radionuclide for the 'theranostic pair' is critical and takes into account not only the type of cytotoxic radiation emission, but also the linear energy transfer (LET), and the physical half-lives. Advances in radiochemistry and radiopharmacy with new radiolabeling techniques and chelators are revolutionizing the field. The landscape of cytotoxic systemic radionuclide treatments has dramatically expanded through the past decades thanks to all these advancements. This article discusses present and promising future theranostic applications for various types of diseases such as thyroid disorders, neuroendocrine tumors (NET), pediatric malignancies, and prostate cancer (PC), and provides an outlook for future perspectives.

  View details for DOI 10.7150/ntno.64141

  View details for PubMedID 34976584

• 68Ga-PSMA11 PET/CT for biochemically recurrent prostate cancer: Influence of dual-time and PMT- vs SiPM-based detectors. Translational oncology Duan, H., Baratto, L., Hatami, N., Liang, T., Mari Aparici, C., Davidzon, G. A., Iagaru, A. 2021; 15 (1): 101293

  Abstract

  OBJECTIVES: 68Ga-PSMA11 PET/CT is excellent for evaluating biochemically recurrent prostate cancer (BCR PC). Here, we compared the positivity rates of dual-time point imaging using a PET/CT scanner (DMI) with silicon photomultiplier (SiPM) detectors and a PET/CT scanner (D690) with photomultiplier tubes (PMT), in patients with BCR PC.METHODS: Fifty-eight patients were prospectively recruited and randomized to receive scans on DMI followed by D690 or vice-versa. Images from DMI were reconstructed using the block sequential regularized expectation maximization (BSREM) algorithm and images from D690 were reconstructed using ordered subset expectation maximization (OSEM), according to the vendor's recommendations. Two readers independently reviewed all images in randomized order, recorded the number and location of lesions, as well as standardized uptake value (SUV) measurements.RESULTS: Twenty-eight patients (group A) had DMI as first scanner followed by D690, while 30 patients (group B) underwent scans in reversed order. Mean PSA was 30±112.9 (range 0.3-600.66)ng/mL for group A and 41.5±213.2 (range 0.21-1170) ng/mL for group B (P=0.796). The positivity rate in group A was 78.6% (22/28 patients) vs. 73.3% (22/30 patients) in group B. Although the performance of the two scanners was equivalent on a per-patient basis, DMI identified 5 additional sites of suspected recurrent disease when used as first scanner. The second scan time point did not reveal additional abnormal uptake.CONCLUSIONS: The delayed time point in 68Ga-PSMA11 PET/CT did not show a higher positivity rate. SiPM-based PET/CT identified additional lesions. Further studies with larger cohorts are needed to confirm these results.

  View details for DOI 10.1016/j.tranon.2021.101293

  View details for PubMedID 34823095

• Pilot-phase PET/CT study targeting integrin alphavbeta6 in pancreatic cancer patients using the cystine-knot peptide-based 18F-FP-R01-MG-F2. European journal of nuclear medicine and molecular imaging Nakamoto, R., Ferri, V., Duan, H., Hatami, N., Goel, M., Rosenberg, J., Kimura, R., Wardak, M., Haywood, T., Kellow, R., Shen, B., Park, W., Iagaru, A., Gambhir, S. S. 2021

  Abstract

  PURPOSE: A novel cystine-knot peptide-based PET radiopharmaceutical, 18F-FP-R01-MG-F2 (knottin), was developed to selectively bind to human integrin alphavbeta6 which is overexpressed in pancreatic cancer. The purpose of this study is to evaluate the safety, biodistribution, dosimetry, and lesion uptake of 18F-FP-R01-MG-F2 in patients with pancreatic cancer.METHODS: Fifteen patients (6 men, 9 women) with histologically confirmed pancreatic cancer were prospectively enrolled and underwent knottin PET/CT between March 2017 and February 2021 (ClinicalTrials.gov Identifier NCT02683824). Vital signs and laboratory results were collected before and after the imaging scans. Maximum standardized uptake values (SUVmax) and mean SUV (SUVmean) were measured in 24 normal tissues and pancreatic cancer lesions for each patient. From the biodistribution data, the organ doses and whole-body effective dose were calculated using OLINDA/EXM software.RESULTS: There were no significant changes in vital signs or laboratory values that qualified as adverse events or serious adverse events. At 1h post-injection, areas of high 18F-FP-R01-MG-F2 uptake included the pituitary gland, stomach, duodenum, kidneys, and bladder (average SUVmean: 9.7-14.5). Intermediate uptake was found in the normal pancreas (average SUVmean: 4.5). Mild uptake was found in the lungs and liver (average SUVmean<1.0). The effective dose was calculated to be 2.538*10-2mSv/MBq. Knottin PET/CT detected all known pancreatic tumors in the 15 patients, although it did not detect small peri-pancreatic lymph nodes of less than 1cm in short diameter in two of three patients who had lymph node metastases at surgery. Knottin PET/CT detected distant metastases in the lungs (n=5), liver (n=4), and peritoneum (n=2), confirmed by biopsy and/or contrast-enhanced CT.CONCLUSION: 18F-FP-R01-MG-F2 is a safe PET radiopharmaceutical with an effective dose comparable to other diagnostic agents. Evaluation of the primary pancreatic cancer and distant metastases with 18F-FP-R01-MG-F2 PET is feasible, but larger studies are required to define the role of this approach.TRIAL REGISTRATION: NCT02683824.

  View details for DOI 10.1007/s00259-021-05595-7

  View details for PubMedID 34729628

• Comparison of a First-in-Class LINAC-Integrated PET System and a Diagnostic PET/CT Scanner. International journal of radiation oncology, biology, physics Surucu, M., Maniyedath, A., Narayanan, M., Han, B., Kovalchuk, N., Gensheimer, M. F., Vitzthum, L., Iagaru, A. H., Ferri, V., Xing, L., Shirvani, S. M., Chang, D. T. 2021; 111 (3S): e515-e516

  Abstract

  PURPOSE/OBJECTIVE(S): The X1 system ("X1") integrates a fully functional Positron Emission Tomography (PET) combined with a fan-beam kVCT system into the architecture of a ring-gantry linear accelerator (LINAC) for biology-guided radiotherapy (BgRT) delivery. The integration of PET into a LINAC framework required design features that deviate from the diagnostic setting. For instance, the X1 houses two opposed 90° PET arcs that rotate at 60 RPM to generate sinogram reconstructed images rather than a static, circumferential array of detectors. To better understand X1 PET performance, we conducted a side-by-side comparison of images of a PET phantom obtained sequentially on the X1 PET subsystem and a traditional PET/CT scanner.MATERIALS/METHODS: An independent quality assurance phantom utilized a custom insert with two-insert targets filled with 18F-fluorodeoxyglucose (FDG) diluted water. Spherical target had a diameter of 22 mm and C-shape geometry consisted of an active volume of 26mm axial length and 255-degree partial annulus with major and minor radii of 27 mm x 12 mm, respectively. The targets were filled with an activity concentration of 9.3 kBq/ml to achieve a target to background ratio of 8:1 simulating the target uptake with hot background in a patient. The phantom was imaged within 30 minutes of preparation on the X1 PET and then immediately transferred to a PET/CT Biograph scanner for a second image. This experiment was repeated three times in separate days to assess reproducibility of PET acquisition. The PET images were visually assessed by the radiation oncologists to ensure the PET signal is within PTV. The PET signals of the targets were also evaluated using the full-width-half-max (FWHM) calculated on left-right (RL), anterior-posterior (AP) and superior-inferior (SI) directions for both targets and compared to the physical dimensions of the cavities.RESULTS: The imaging acquisition tests were successfully completed on all three days for both systems, as per the prescribed workflow. In all experiments, radiation oncologists verified that the PET avid area were within the PTV in both systems. Average FWHM results of the 22 mm spherical target on X1 PET were 24.5, 21.7 and 17.0 mm as compared to 20.0, 20.0 and 18.2 mm for PET/CT in LR, AP and SI directions, respectively. For the C-shape object X1 PET resulted in 18.8, 19.5, 21.8 and 25.0 mm whereas the PET/CT resulted in 12.7, 13.2, 13.2 and 24.7 mm FWHMs for the two RL C-shape legs, AP and SI directions, respectively as compared to 15-, 15-, 15- and 26-mm physical dimensions.CONCLUSION: The X1 PET subsystem - which utilizes dual PET arcs and a sinogram image reconstruction algorithm in order to integrate into a LINAC architecture - generates images that are qualitatively comparable to a traditional PET scanner. In general, X1 FWHM results were slightly larger and PET/CT ones were smaller than the physical dimensions in axial plane. Both systems slightly underestimated the target size in SI direction.

  View details for DOI 10.1016/j.ijrobp.2021.07.1411

  View details for PubMedID 34701636

• Initial Evaluation of Biology-Guided Radiotherapy (BgRT) Plans Generated Using PET Acquired on the First Installation of New System Surucu, M., Narayanan, M., Han, B., Khan, S., Da Silva, A., Maniyedath, A., Yeung, T., Shirvani, S., Kuduvalli, G., Gensheimer, M. F., Vitzthum, L., Iagaru, A. H., Xing, L., Chang, D. T., Kovalchuk, N. ELSEVIER SCIENCE INC. 2021: E516

  View details for Web of Science ID 000715803801069

• Comparison of a First-in-Class LINAC-Integrated PET System and a Diagnostic PET/CT Scanner Surucu, M., Maniyedath, A., Narayanan, M., Han, B., Kovalchuk, N., Gensheimer, M. F., Vitzthum, L., Iagaru, A. H., Ferri, V., Xing, L., Shirvani, S. M., Chang, D. T. ELSEVIER SCIENCE INC. 2021: E515-E516

  View details for Web of Science ID 000715803801068

• Initial Evaluation of Biology-Guided Radiotherapy (BgRT) Plans Generated Using PET Acquired on the First Installation of New System. International journal of radiation oncology, biology, physics Surucu, M., Narayanan, M., Han, B., Khan, S., Da Silva, A., Maniyedath, A., Yeung, T., Shirvani, S., Kuduvalli, G., Gensheimer, M. F., Vitzthum, L., Iagaru, A. H., Xing, L., Chang, D. T., Kovalchuk, N. 2021; 111 (3S): e516

  Abstract

  PURPOSE/OBJECTIVE(S): To evaluate Biology-guided Radiotherapy (BgRT) plans generated using PET data acquired on the first installation of the Reflexion X1 system. BgRT treatment planning optimizes for fluence indirectly by calculating firing filters that best translate the X1 acquired PET image to the fluences that deliver the prescribed radiation dose. During a treatment session, the firing filters are applied to limited time sampled (LTS) PET images to calculate delivery fluences.MATERIALS/METHODS: An FDG fillable phantom insert that consists of a 22 mm diameter spherical target (PTV1, ball) and a C-shape object (PTV2 with 26mm axial length, 255° partial annulus with major and minor radii of 27 mm and 12 mm) was imaged using a CT Simulator to create planning contours. The water filled insert surrounding these objects was filled with FDG to simulate a warm background. Both targets were filled with FDG, simulating a target to background ratio of 8:1. Two different BgRT treatment plans were generated for PTV1 simulating homogenous uptake, and PTV2 with an inhomogeneous FDG uptake due to necrosis (a cylinder encompassing the C shape PET avid object). A structure that is 12.5 mm away from these targets was used to simulate OAR. Two PET/CT imaging acquisitions were performed on the RefleXion X1 masking the signal outside of each target plus 10 mm margin. Two different BgRT plans were generated prescribing 50 Gy delivered in 5 fractions to each target, separately. The quality of each treatment plan was evaluated based on PTV coverage, Conformity Index at 50% and 80% isodose lines (CI50, CI80) and OAR sparing. Both BgRT plans then delivered to the independent quality assurance tool for patient specific QA verification where the 3%/3 mm gamma criteria was used.RESULTS: BgRT plans for both homogenous and heterogenous FDG uptake targets were created successfully. Prescription dose coverages were 94.2% and 96.3% for PTV1 and PTV2, respectively. The maximum OAR doses were 30.9 and 33.0 Gy and average OAR doses were 14.4 and 20.1 Gy for PTV1 and PTV2 plans, respectively. CI50 were 7.7 and 6.8 where CI80 were 2.5 and 2.6 for PTV1 and PTV2 plans. The patient specific QA passed with 100 % for both plans.CONCLUSION: This is the first report of the BgRT plan creation and QA delivery using a clinical installation of the Reflexion X1 system, opening the potential towards BgRT dose delivery using the real time FDG uptake measurements to biologically guide active radiation beam delivery. The X1 system was able to optimize and deliver the BgRT plans for both homogenous and heterogenous FDG uptake scenarios. BgRT is a new paradigm of dose optimization, where a new set of optimization and evaluation approaches will be needed.

  View details for DOI 10.1016/j.ijrobp.2021.07.1412

  View details for PubMedID 34701638

• 18F DCFPyL PET Acquisition, Interpretation and Reporting: Suggestions Post Food and Drug Administration Approval. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Song, H., Iagaru, A., Rowe, S. P. 2021

  Abstract

  18F-DCFPyL was recently approved by the FDA for evaluation prior to definitive therapy and for biochemical recurrence. Here we focus on the key data that justify the clinical use of 18F-DCFPyL, as well as those aspects of protocol implementation and image interpretation that are important to the nuclear medicine physicians and radiologists who will interpret 18F-DCFPyL PET/CT and PET/MR scans.

  View details for DOI 10.2967/jnumed.121.262989

  View details for PubMedID 34531266

• A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2 Induced Glycolytic Reprogramming in Glioblastoma. Clinical cancer research : an official journal of the American Association for Cancer Research Beinat, C., Patel, C. B., Haywood, T., Murty, S., Naya, L., Castillo, J. B., Reyes, S. T., Phillips, M., Buccino, P., Shen, B., Park, J. H., Koran, M. E., Alam, I. S., James, M. L., Holley, D., Halbert, K., Gandhi, H., He, J. Q., Granucci, M., Johnson, E., Liu, D. D., Uchida, N., Sinha, R., Chu, P., Born, D. E., Warnock, G. I., Weissman, I., Hayden Gephart, M., Khalighi, M. M., Massoud, T. F., Iagaru, A., Davidzon, G., Thomas, R., Nagpal, S., Recht, L. D., Gambhir, S. S. 2021

  Abstract

  PURPOSE: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel positron emission tomography (PET) tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and GBM patients.EXPERIMENTAL DESIGN: [18F]DASA-23 was synthesized with a molar activity of 100.47 {plus minus} 29.58 GBq/mol and radiochemical purity >95%. We performed initial testing of [18F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next we produced [18F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers, and a pilot cohort of glioma patients.RESULTS: In mouse imaging studies, [18F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio (TBR) of 3.6 {plus minus} 0.5. In human volunteers, [18F]DASA-23 crossed the intact blood-brain barrier and was rapidly cleared. In GBM patients, [18F]DASA-23 successfully outlined tumors visible on contrast-enhanced magnetic resonance imaging (MRI). The uptake of [18F]DASA-23 was markedly elevated in GBMs compared to normal brain, and it identified a metabolic non-responder within 1-week of treatment initiation.CONCLUSIONS: We developed and translated [18F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [18F]DASA-23 to assess its utility for imaging therapy-induced normalization of aberrant cancer metabolism.

  View details for DOI 10.1158/1078-0432.CCR-21-0544

  View details for PubMedID 34475101

• Pilot phase study of F-18-FP-R(0)1-MG-F2 PET in pancreatic cancer patients Nakamoto, R., Ferri, V., Duan, H., Hatami, N., Goel, M., Rosenberg, J., Kimura, R., Wardak, M., Haywood, T., Kellow, R., Shen, B., Park, W., Iagaru, A. SPRINGER. 2021: S301-S302

  View details for Web of Science ID 000709355001008

• Clinical Applications of PET/MR Imaging. Radiologic clinics of North America Moradi, F., Iagaru, A., McConathy, J. 2021; 59 (5): 853-874

  Abstract

  PET/MR imaging is in routine clinical use and is at least as effective as PET/CT for oncologic and neurologic studies with advantages with certain PET radiopharmaceuticals and applications. In addition, whole body PET/MR imaging substantially reduces radiation dosages compared with PET/CT which is particularly relevant to pediatric and young adult population. For cancer imaging, assessment of hepatic, pelvic, and soft-tissue malignancies may benefit from PET/MR imaging. For neurologic imaging, volumetric brain MR imaging can detect regional volume loss relevant to cognitive impairment and epilepsy. In addition, the single-bed position acquisition enables dynamic brain PET imaging without extending the total study length which has the potential to enhance the diagnostic information from PET.

  View details for DOI 10.1016/j.rcl.2021.05.013

  View details for PubMedID 34392923

• PROSPECTIVE STUDY OF (68)GA-RM2 PET/MRI IN PATIENTS WITH BIOCHEMICALLY RECURRENT PROSTATE CANCER AND NEGATIVE CONVENTIONAL IMAGING Baratto, L., Song, H., Duan, H., Moradi, F., Davidzon, G., Iagaru, A. LIPPINCOTT WILLIAMS & WILKINS. 2021: E1178

  View details for Web of Science ID 000693689000848

• PROSPECTIVE EVALUATION OF F-18-DCFPYL PET/CT IN BIOCHEMICALLY RECURRENT PROSTATE CANCER: ANALYSIS OF F-18-DCFPYL UPTAKE IN POSSIBLE EXTRA-PELVIC OLIGOMETASTASES Song, H., Nguyen, J., Moradi, F., Aparici, C., Franc, B., Davidzon, G., Iagaru, A. LIPPINCOTT WILLIAMS & WILKINS. 2021: E1177-E1178

  View details for Web of Science ID 000693689000847

• Association of Time Since Administration of Pegylated G-CSF (Pegfilgrastim) and Bone Marrow Uptake on FDG PET/CT: Determination of a Minimum Interval. AJR. American journal of roentgenology Minamimoto, R., Baratto, L., Iagaru, A. 2021

  Abstract

  Background: Pegfilgrastim administration after chemotherapy increases bone marrow and spleen FDG uptake. Consensus is lacking regarding the optimal interval between pegfilgrastim administration and FDG PET/CT. Objective: To assess the association between bone marrow and spleen uptake and the interval between pegfilgrastim administration and FDG PET/CT. Methods: This retrospective study included 70 oncology patients (mean age, 64±12 years; 48 male, 22 female) on chemotherapy who underwent FDG PET/CT (study scan) within 35 days after pegfilgrastim administration and who underwent additional FDG PET/CT at least 4 months before pegfilgrastim initiation or at least 3 months after last pegfilgrastim administration (reference scan). A nuclear medicine physician recorded SUVmean for normal osseous structures and spleen and assessed bone marrow uptake using a 4-point visual scale (1=no abnormal uptake, 2=clinically insignificant uptake, 3=clinically significant uptake possibly interfering with interpretation, 4=clinically significant uptake expected to interfere with interpretation). Results: Percentage change in SUVmean between reference and study scans increased (p<.05) as the interval increased for five sites (i.e., percentage change for patients with interval of 7-13 days versus 29-35 days of 32.3±18.2 versus 11.5±17.3 for cervical vertebrae, 42.2±18.3 versus 21.3±14.2 for thoracic vertebrae, 47.2±19.8 versus 19.1±13.9 for lumbar vertebrae, 51.1±25.8 versus 12.7±11.3 for pelvis, and 53.0±25.6 versus 4.4±14.1 for lower extremity); percentage change was not associated with the interval for upper extremity or spleen (p>.05). Visual uptake score of 4 was observed in days 7-21, score of 3 in days 12-22, score of 2 in days 12-28, and score of 1 in days 14-35. Percentage of patients with score 3 or 4 was 94.4% for days 7-13, 58.1% for 14-21 days, 4.8% for 22-28 days, and 0% for 29-35 days. A total of 71.4% of patients showed score 3 or 4 on day 7-21, whereas 3.2% showed score of 3 and 0.0% showed score of 4 on day 22-35. Conclusion: Visual uptake score of 3 or 4 was consistently observed throughout an approximately 3 week interval following pegfilgrastim administration, without any such case beyond 22 days. Clinical Impact: We recommend a preferred interval of at least 3 weeks after pegfilgrastim administration prior to PET/CT.

  View details for DOI 10.2214/AJR.21.26480

  View details for PubMedID 34467784

• A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer Duan, H., Ferri, V., Ghanouni, P., Daniel, B., Hatami, N., Davidzon, G. A., Aparici, C., Thong, A., Sonn, G. A., Iagaru, A. SPRINGER. 2021: S204

  View details for Web of Science ID 000709355000333

• A Pilot Study of Ga-68-PSMA11 and Ga-68-RM2 PET/MRI for Evaluation of Prostate Cancer Response to High Intensity Focused Ultrasound (HIFU) Therapy Duan, H., Ghanouni, P., Hatami, N., Davidzon, G. A., Aparici, C., Thong, A., Sonn, G. A., Iagaru, A. SPRINGER. 2021: S205-S206

  View details for Web of Science ID 000709355000336

• To Scan or Not to Scan: An Unnecessary Dilemma for PSMA Radioligand Therapy. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Srinivas, S., Iagaru, A. 2021

  View details for DOI 10.2967/jnumed.121.263035

  View details for PubMedID 34446452

• Reduced Acquisition Time Per Bed Position for PET/MRI Using 68Ga-RM2 or 68Ga-PSMA11 in Patients With Prostate Cancer: A Retrospective Analysis. AJR. American journal of roentgenology Duan, H., Baratto, L., Hatami, N., Liang, T., Levin, C. S., Khalighi, M. M., Iagaru, A. 2021

  Abstract

  Background: Growing clinical adoption of PET/MRI for prostate cancer (PC) evaluation has increased interest in reducing PET/MRI scan times. Reducing acquisition time per bed position below current times of at least 5 minutes would allow shorter examination lengths. Objective: To evaluate the effect of different reduced PET acquisition times in patients with PC who underwent 68Ga-PSMA11 or 68Ga-RM2 PET/MRI using highly sensitive silicon photomultiplier-based PET detectors. Methods: This study involved retrospective review of men with PC who underwent PET/MRI as part of one of two prospective trials. Fifty men (mean age, 69.9±6.8 years) who underwent 68Ga-RM2 PET/MRI and 50 men (66.6±5.7 years) who underwent 68Ga-PSMA11 PET/MRI were included. PET/MRI used a time-of-flight-enabled system with silicon photomultiplier-based detectors. Acquisition time was 4 minutes per bed position. PET data were reconstructed using acquisition times of 30 seconds, 1 minute, 2 minutes, 3 minutes, and 4 minutes. Three readers independently assessed image quality for each reconstruction using 1-5 scale (1=non-diagnostic; 5=excellent quality). One reader measured SUVmax for up to 6 lesions per patient. Two readers independently assessed lesion conspicuity using 1-3 scale (1=not visualized; 3=definitely visualized). Results: Mean image quality across readers at 30 seconds, 1 minutes, 2 minutes, 3 minutes, and 4 minutes was, for 68Ga-RM2 PET/MRI, 1.0±0.2 to 1.7±0.7, 2.0±0.3 to 2.6±0.8, 3.1±0.5 to 3.9±0.8, 4.6±0.6 to 4.7±0.6, and 4.8±0.4 to 4.8±0.5, respectively, and for 68Ga-PSMA11 PET/MRI was 1.2±0.4 to 1.8±0.6, 2.2±0.4 to 2.8±0.7, 3.6±0.6 to 4.1±0.8, 4.8±0.4 to 4.9±0.4, and 4.9±0.3 to 5.0±0.2, respectively. Mean lesion SUVmax for 68Ga-RM2 PET/MRI was 11.1±12.4, 10.2±11.7, 9.6±11.3, 9.5±11.6, and 9.4±11.6, respectively, and for 68Ga-PSMA11 PET/MRI was 14.7±8.2, 12.9±7.4, 12.1±7.8, 11.7±7.9, and 11.6±7.9, respectively. Mean lesion conspicuity (reader 1/reader 2) was, for 68Ga-RM2 PET/MRI, 2.4±0.5/2.7±0.5, 2.9±0.3/2.9±0.3, 3.0±0.0/3.0±0.0, 3.0±0.0/3.0±0.0, and 3.0±0.0/3.0±0.0, respectively, and for 68Ga-PSMA11 PET/MRI was 2.6±0.5/2.8±0.4, 3.0±0.2/2.9±0.3, 3.0±0.1/3.0±0.2, 3.0±0.0/3.0±0.0, and 3.0±0.0/3.0±0.0, respectively. Conclusion: Our data support routine 3 minute acquisitions, which provided very similar results as 4 minute acquisitions. Two minute acquisition, though somewhat lowering quality, provided acceptable performance and warrants consideration. Clinical Impact: When evaluating PC using modern PET/MRI equipment, time per bed position may be reduced compared with historically used times.

  View details for DOI 10.2214/AJR.21.25961

  View details for PubMedID 34406051

• Prostate cancer: Molecular imaging and MRI. European journal of radiology Moradi, F., Farolfi, A., Fanti, S., Iagaru, A. 2021; 143: 109893

  Abstract

  The role of molecular imaging in initial evaluation of men with presumed or established diagnosis of prostate cancer and work up of biochemical recurrence and metastatic disease is rapidly evolving due to superior diagnostic performance compared to anatomic imaging. However, variable tumor biology and expression of transmembrane proteins or metabolic alterations poses a challenge. We review the evidence and controversies with emphasis on emerging PET radiopharmaceuticals and experience on clinical utility of PET/CT and PET/MRI in diagnosis and management of prostate cancer.

  View details for DOI 10.1016/j.ejrad.2021.109893

  View details for PubMedID 34391061

• 2021 SNMMI Highlights Lecture: General Nuclear Medicine. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Iagaru, A. 2021; 62 (8): 12N-17N

  View details for PubMedID 34330743

• 2021 SNMMI Highlights Lecture: General Nuclear Medicine JOURNAL OF NUCLEAR MEDICINE Iagaru, A. 2021; 62 (8): 12N-17N

  View details for Web of Science ID 000711570000002

• New PET technologies - embracing progress and pushing the limits. European journal of nuclear medicine and molecular imaging Aide, N., Lasnon, C., Kesner, A., Levin, C. S., Buvat, I., Iagaru, A., Hermann, K., Badawi, R. D., Cherry, S. R., Bradley, K. M., McGowan, D. R. 2021

  View details for DOI 10.1007/s00259-021-05390-4

  View details for PubMedID 34081153

• Positron Emission Tomography (PET) Characterization for Biology-Guided Radiotherapy (BgRT) Hu, Z., Narayanan, M., Ferri, V., Iagaru, A., Kovalchuk, N., Han, B., Xing, L., Vitzthum, L., Olcott, P., Bieniosek, M., Laurence, T., Shirvani, S., Chang, D., Surucu, M. WILEY. 2021

  View details for Web of Science ID 000673145401292

• Results of a Prospective Trial to Compare 68Ga-DOTA-TATE with SiPM-Based PET/CT vs. Conventional PET/CT in Patients with Neuroendocrine Tumors. Diagnostics (Basel, Switzerland) Baratto, L., Toriihara, A., Hatami, N., Aparici, C. M., Davidzon, G., Levin, C. S., Iagaru, A. 2021; 11 (6)

  Abstract

  We prospectively enrolled patients with neuroendocrine tumors (NETs). They underwent a single 68Ga-DOTA-TATE injection followed by dual imaging and were randomly scanned using first either the conventional or the silicon photomultiplier (SiPM) positron emission tomography/computed tomography (PET/CT), followed by imaging using the other system. A total of 94 patients, 44 men and 50 women, between 35 and 91 years old (mean ± SD: 63 ± 11.2), were enrolled. Fifty-two out of ninety-four participants underwent SiPM PET/CT first and a total of 162 lesions were detected using both scanners. Forty-two out of ninety-four participants underwent conventional PET/CT first and a total of 108 lesions were detected using both scanners. Regardless of whether SiPM-based PET/CT was used first or second, maximum standardized uptake value (SUVmax) of lesions measured on SiPM was on average 20% higher when comparing two scanners with all enrolled patients, and the difference was statistically significant. SiPM-based PET/CT detected 19 more lesions in 13 patients compared with conventional PET/CT. No lesions were only identified by conventional PET/CT. In conclusion, we observed higher SUVmax for lesions measured from SiPM PET/CT compared with conventional PET/CT regardless of the order of the scans. SiPM PET/CT allowed for identification of more lesions than conventional PET/CT. While delayed imaging can lead to higher SUVmax in cancer lesions, in the series of lesions identified when SiPM PET/CT was used first, this was not the case; therefore, the data suggest superior performance of the SiPM PET/CT scanner in visualizing and quantifying lesions.

  View details for DOI 10.3390/diagnostics11060992

  View details for PubMedID 34070751

• Metastatic and sentinel lymph node mapping using intravenously delivered Panitumumab-IRDye800CW. Theranostics Krishnan, G., van den Berg, N. S., Nishio, N., Juniper, G., Pei, J., Zhou, Q., Lu, G., Lee, Y. J., Ramos, K., Iagaru, A. H., Baik, F. M., Colevas, A. D., Martin, B. A., Rosenthal, E. L. 2021; 11 (15): 7188-7198

  Abstract

  Rationale: Sentinel lymph node biopsy (SLNB) is a well-established minimally invasive staging procedure that maps the spread of tumour metastases from their primary site to the regional lymphatics. Currently, the procedure requires the local peri-tumoural injection of radiolabelled and/or optical agents, and is therefore operator dependent, disruptive to surgical workflow and restricted largely to a small subset of malignancies that can be readily accessed externally for local tracer injection. The present study set out to determine whether intravenous (IV) infusion of a tumor-targeted tracer could identify sentinel and metastatic lymph nodes (LNs) in order to overcome these limitations. Methods: We examined 27 patients with oral squamous cell carcinoma (OSCC), 18 of whom were clinically node negative (cN0). Patients were infused intravenously with 50mg of Panitumumab-IRDye800CW prior to surgical resection of their primary tumour with neck dissection and/or SLNB. Lymphadenectomy specimens underwent fluorescence molecular imaging to evaluate tracer distribution to LNs. Results: A total of 960 LNs were analysed, of which 34 (3.5%) contained metastatic disease. Panitumumab-IRDye800CW preferentially localized to metastatic and sentinel LNs as evidenced by a higher fluorescent signal relative to other lymph nodes. The median MFI of metastatic LNs was significantly higher than the median MFI of benign LNs (0.06 versus 0.02, p < 0.05). Furthermore, selecting the highest five fluorescence intensity LNs from individual specimens resulted in 100% sensitivity, 85.8% specificity and 100% negative predictive value (NPV) for the detection of occult metastases and 100% accuracy for clinically staging the neck. In the cN+ cohort, assessment of the highest 5 fluorescence LNs per patient had 87.5% sensitivity, 93.2% specificity and 99.1% NPV for the detection of metastatic nodes. Conclusion: When intravenously infused, a tumour-targeted tracer localized to sentinel and metastatic lymph nodes. Further validation of an IV tumor-targeted tracer delivery approach for SLNB could dramatically change the practice of SLNB, allowing its application to other malignancies where the primary tumour is not accessible for local tracer injection.

  View details for DOI 10.7150/thno.55389

  View details for PubMedID 34158844

  View details for PubMedCentralID PMC8210603

• PSMA-targeted imaging with F-18-DCFPyL-PET/CT in patients (pts) withbiochemically recurrent prostate cancer (PCa): A phase 3 study (CONDOR)-A subanalysis of correct localization rate (CLR) and positive predictive value (PPV) by standard of truth. Pouliot, F., Gorin, M. A., Rowe, S. P., Saperstein, L., Josephson, D., Carroll, P. R., Wong, J. C., Pantel, A. R., Cho, S. Y., Gage, K. L., Piert, M., Iagaru, A., Pollard, J. H., Wong, V., Jensen, J., Stambler, N., Morris, M. J., Siegel, B. A. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.5023

  View details for Web of Science ID 000708120603044

• Prognostic relevance of the hexosamine biosynthesis pathway activation in leiomyosarcoma. NPJ genomic medicine Tolwani, A., Matusiak, M., Bui, N., Forgo, E., Varma, S., Baratto, L., Iagaru, A., Lazar, A. J., van de Rijn, M., Przybyl, J. 2021; 6 (1): 30

  Abstract

  Metabolic reprogramming of tumor cells and the increase of glucose uptake is one of the hallmarks of cancer. In order to identify metabolic pathways activated in leiomyosarcoma (LMS), we analyzed transcriptomic profiles of distinct subtypes of LMS in several datasets. Primary, recurrent and metastatic tumors in the subtype 2 of LMS showed consistent enrichment of genes involved in hexosamine biosynthesis pathway (HBP). We demonstrated that glutamine-fructose-6-phosphate transaminase 2 (GFPT2), the rate-limiting enzyme in HBP, is expressed on protein level in a subset of LMS and the expression of this enzyme is frequently retained in patient-matched primary and metastatic tumors. In a new independent cohort of 327 patients, we showed that GFPT2 is associated with poor outcome of uterine LMS but not extra-uterine LMS. Based on the analysis of a small group of patients studied by 18F-FDG-PET imaging, we propose that strong expression of GFPT2 in primary LMS may be associated with high metabolic activity. Our data suggest that HBP is a potential new therapeutic target in one of the subtypes of LMS.

  View details for DOI 10.1038/s41525-021-00193-w

  View details for PubMedID 33941787

• A Pilot Study of68Ga-PSMA11 PET/MRI and68GaRM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer Duan, H., Ferri, V., Ghanouni, P., Daniel, B., Hatami, N., Davidzon, G., Aparici, C., Moradi, F., Thong, A., Sonn, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2021

  View details for Web of Science ID 000713713600481

• A Phase 3 study of F-18-DCFPyL-PET/CT in Patients with Biochemically Recurrent Prostate Cancer (CONDOR): An Analysis of Disease Detection Rate and Positive Predictive Value (PPV) by Anatomic Region Rowe, S., Gorin, M., Saperstein, L., Pouliot, F., Josephson, D., Carroll, P., Wong, J., Pantel, A., Piert, M., Gage, K., Cho, S., Iagaru, A., Pollard, J., Wong, V., Jensen, J., Stambler, N., Morris, M., Siegel, B. SOC NUCLEAR MEDICINE INC. 2021

  View details for Web of Science ID 000713713600122

• Initial Clinical Evaluation of [F-18]DASA-23, a PET Imaging Tracer for Evaluation of Aberrantly Expressed Pyruvate Kinase M2 in Glioblastoma Beinat, C., Patel, C., Haywood, T., Naya, L., Castillo, J., Shen, B., Massoud, T., Iagaru, A., Davidzon, G., Recht, L., Gambhir, S. SOC NUCLEAR MEDICINE INC. 2021

  View details for Web of Science ID 000713713600098

• Perfusion Only Scans with and without SPECT/CT in the Era of COVID-19 Zhang, R., Moradi, F., Aparici, C., Davidzon, G., Nguyen, J., Iagaru, A., Franc, B. SOC NUCLEAR MEDICINE INC. 2021

  View details for Web of Science ID 000713713600506

• Biodistribution and Safety of F-18-FP-R(0)1-MG-F2 Knottin PET Tracer in Patients with Pancreatic Cancer Nakamoto, R., Duan, H., Ferri, V., Hatami, N., Goel, M., Kimura, R., Wardak, M., Haywood, T., Shen, B., Park, W., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2021

  View details for Web of Science ID 000713713600186

• Pilot Comparison of F-18-FP-R01-MG-F2 and F-18-FDG PET in Patients with Pancreatic Cancer Nakamoto, R., Duan, H., Ferri, V., Hatami, N., Goel, M., Kimura, R., Wardak, M., Haywood, T., Shen, B., Park, W., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2021

  View details for Web of Science ID 000713713600182

• Unconventional non-amino acidic PET radiotracers for molecular imaging in gliomas. European journal of nuclear medicine and molecular imaging Laudicella, R., Quartuccio, N., Argiroffi, G., Alongi, P., Baratto, L., Califaretti, E., Frantellizzi, V., De Vincentis, G., Del Sole, A., Evangelista, L., Baldari, S., Bisdas, S., Ceci, F., Iagaru, A., Young Italian Association of Nuclear Medicine (AIMN) group 2021

  Abstract

  PURPOSE: The objective of this review was to explore the potential clinical application of unconventional non-amino acid PET radiopharmaceuticals in patients with gliomas.METHODS: A comprehensive search strategy was used based on SCOPUS and PubMed databases using the following string: ("perfusion" OR "angiogenesis" OR "hypoxia" OR "neuroinflammation" OR proliferation OR invasiveness) AND ("brain tumor" OR "glioma") AND ("Positron Emission Tomography" OR PET). From all studies published in English, the most relevant articles were selected for this review, evaluating the mostly used PET radiopharmaceuticals in research centers, beyond amino acid radiotracers and 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), for the assessment of different biological features, such as perfusion, angiogenesis, hypoxia, neuroinflammation, cell proliferation, tumor invasiveness, and other biological characteristics in patients with glioma.RESULTS: At present, the use of non-amino acid PET radiopharmaceuticals specifically designed to assess perfusion, angiogenesis, hypoxia, neuroinflammation, cell proliferation, tumor invasiveness, and other biological features in glioma is still limited.CONCLUSION: The use of investigational PET radiopharmaceuticals should be further explored considering their promising potential and studies specifically designed to validate these preliminary findings are needed. In the clinical scenario, advancements in the development of new PET radiopharmaceuticals and new imaging technologies (e.g., PET/MR and the application of the artificial intelligence to medical images) might contribute to improve the clinical translation of these novel radiotracers in the assessment of gliomas.

  View details for DOI 10.1007/s00259-021-05352-w

  View details for PubMedID 33851243

• High-specific-activity 131I-MIBG vs 177Lu-DOTATATE targeted radionuclide therapy for metastatic pheochromocytoma and paraganglioma. Clinical cancer research : an official journal of the American Association for Cancer Research Jha, A., Taieb, D., Carrasquillo, J. A., Pryma, D. A., Patel, M., Millo, C., de Herder, W. W., Del Rivero, J., Crona, J., Shulkin, B. L., Virgolini, I., Chen, A. P., Mittal, B. R., Basu, S., Dillon, J. S., Hope, T. A., Mari Aparici, C., Iagaru, A., Hicks, R. J., Avram, A. M., Strosberg, J. R., Civelek, A. C., Lin, F. I., Pandit-Taskar, N., Pacak, K. 2021

  Abstract

  Targeted radionuclide therapies using 131I-metaiodobenzylguanidine (131I-MIBG) and peptide receptor radionuclide therapy (177Lu or 90Y) represent several of the therapeutic options in the management of metastatic or inoperable pheochromocytoma and/or paraganglioma (PPGL). Recently, high-specific-activity-131I-MIBG therapy was approved by the FDA and both 177Lu-DOTATATE and 131I-MIBG therapy were recommended by the National Comprehensive Cancer Network (NCCN) guidelines for the treatment of metastatic PPGL. However, a clinical dilemma often arises in the selection of targeted radionuclide therapy, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatostatin receptor imaging. In order to address this problem, we assembled a group of international experts including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with targeted radionuclide therapies in order to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic PPGL. This manuscript aims to summarize the survival outcomes of the available targeted radionuclide therapies, discuss personalized treatment strategies based on functional imaging scans, address practical issues including regulatory approvals, and compare toxicities and risk factors across treatments. Further, it discusses the emerging targeted radionuclide therapies.

  View details for DOI 10.1158/1078-0432.CCR-20-3703

  View details for PubMedID 33685867

• PSMA- and GRPR-targeted PET: Results from 50 Patients with Biochemically Recurrent Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Baratto, L., Song, H., Duan, H., Hatami, N., Bagshaw, H., Buyyounouski, M., Hancock, S., Shah, S. A., Srinivas, S., Swift, P., Moradi, F., Davidzon, G. A., Iagaru, A. 2021

  Abstract

  Rationale: Novel radiopharmaceuticals for positron emission tomography (PET) are evaluated for the diagnosis of biochemically recurrent prostate cancer (BCR PC). Here, we compare the gastrin releasing peptide receptors (GRPR) - targeting 68Ga-RM2 with the prostate specific membrane antigen (PSMA) - targeting 68Ga-PSMA11 and 18F-DCFPyL. Methods: Fifty patients had both 68Ga-RM2 PET/MRI and 68Ga-PSMA11 PET/CT (n = 23) or 18F-DCFPyL PET/CT (n = 27) at an interval ranging from 1 to 60 days (mean±SD: 15.8±17.7). Maximum standardized uptake values (SUVmax) were collected for all lesions. Results: RM2 PET was positive in 35 and negative in 15 of the 50 patients. PSMA PET was positive in 37 and negative in 13 of the 50 patients. Both scans detected 70 lesions in 32 patients. Forty-three lesions in 18 patients were identified only on one scan: 68Ga-RM2 detected 7 more lesions in 4 patients, while PSMA detected 36 more lesions in 13 patients. Conclusion: 68Ga-RM2 remains a valuable radiopharmaceutical even when compared with the more widely used 68Ga-PSMA11/18F-DCFPyL in the evaluation of BCR PC. Larger studies are needed to verify that identifying patients for whom these two classes of radiopharmaceuticals are complementary may ultimately allow for personalized medicine.

  View details for DOI 10.2967/jnumed.120.259630

  View details for PubMedID 33674398

• Renal and Hepatotoxicity of Peptide Receptor Radionuclide Therapy (PRRT) - A Single Institution Experience Duan, H., Ferri, V., Kunz, P., Davidzon, G., Nguyen, J., Moradi, F., Franc, B., Iagaru, A., Aparici, C. LIPPINCOTT WILLIAMS & WILKINS. 2021: 456-457

  View details for Web of Science ID 000639230600093

• Single Institution Experience With Peptide Receptor Radionuclide Therapy (PRRT) in Neuroendocrine Tumors (NET) Duan, H., Ferri, V., Kunz, P., Davidzon, G., Nguyen, J., Moradi, F., Franc, B., Iagaru, A., Aparici, C. LIPPINCOTT WILLIAMS & WILKINS. 2021: 456

  View details for Web of Science ID 000655285500090

• Renal and Hepatotoxicity of Peptide Receptor Radionuclide Therapy (PRRT) - A Single Institution Experience Duan, H., Ferri, V., Kunz, P., Davidzon, G., Nguyen, J., Moradi, F., Franc, B., Iagaru, A., Aparici, C. LIPPINCOTT WILLIAMS & WILKINS. 2021: 456-457

  View details for Web of Science ID 000655285500093

• Hematotoxicity of Peptide Receptor Radionuclide Therapy (PRRT) - A Single Institution Experience Duan, H., Ferri, V., Kunz, P., Davidzon, G., Moradi, F., Nguyen, J., Franc, B., Iagaru, A., Aparici, C. LIPPINCOTT WILLIAMS & WILKINS. 2021: 456

  View details for Web of Science ID 000655285500092

• Hematotoxicity of Peptide Receptor Radionuclide Therapy (PRRT) - A Single Institution Experience Duan, H., Ferri, V., Kunz, P., Davidzon, G., Moradi, F., Nguyen, J., Franc, B., Iagaru, A., Aparici, C. LIPPINCOTT WILLIAMS & WILKINS. 2021: 456

  View details for Web of Science ID 000639230600092

• Single Institution Experience With Peptide Receptor Radionuclide Therapy (PRRT) in Neuroendocrine Tumors (NET) Duan, H., Ferri, V., Kunz, P., Davidzon, G., Nguyen, J., Moradi, F., Franc, B., Iagaru, A., Aparici, C. LIPPINCOTT WILLIAMS & WILKINS. 2021: 456

  View details for Web of Science ID 000639230600090

• Diagnostic Performance of 18F-DCFPyL-PET/CT in Men with Biochemically Recurrent Prostate Cancer: Results from the CONDOR Phase 3, Multicenter Study. Clinical cancer research : an official journal of the American Association for Cancer Research Morris, M. J., Rowe, S. P., Gorin, M. A., Saperstein, L., Pouliot, F., Josephson, D. Y., Wong, J. Y., Pantel, A. R., Cho, S. Y., Gage, K. L., Piert, M. R., Iagaru, A., Pollard, J. H., Wong, V., Jensen, J., Lin, T., Stambler, N., Carroll, P., Siegel, B. A., Wibmer, A. G., Durack, J. C., Solomon, S. B., Harb, R., Pucar, D., Sprenkle, P., Beauregard, J., Beaulieu, A., Buteau, F., Yamauchi, D., Glaser, S., Dorff, T. B., Narayan, V., Fillare, M. A., Schubert, E., Cooley, G., Morris, Z. S., Langeland, M., Pow-Sang, J. M., Yamoah, K., Alva, A. S., Reichert, Z., Spratt, D., Davidzon, G., Mari Aparici, C., Moradi, F., Tracy, C., Behr, S., Nguyen, H. G., Simko, J. P., Jennings, J. W., Michalski, J. M., Pachynski, R. K. 2021

  Abstract

  PURPOSE: Current FDA-approved imaging modalities are inadequate for localizing prostate cancer biochemical recurrence (BCR). 18F-DCFPyL is a highly selective, small-molecule PSMA-targeted PET radiotracer. CONDOR was a prospective study designed to determine the performance of 18F-DCFPyL-PET/CT in patients with BCR and uninformative standard imaging.METHODS: Men with rising PSA {greater than or equal to}0.2 ng/mL after prostatectomy or {greater than or equal to}2 ng/mL above nadir after radiation therapy were eligible. The primary endpoint was correct localization rate (CLR) defined as positive predictive value with an additional requirement of anatomic lesion co-localization between 18F-DCFPyL-PET/CT and a composite standard of truth (SOT). The SOT consisted of, in descending priority: 1) histopathology, 2) subsequent correlative imaging findings, or 3) post-radiation PSA response. The trial was considered a success if the lower bound of the 95% confidence interval for CLR exceeded 20% for 2 of 3 18F‑DCFPyL-PET/CT readers. Secondary endpoints included change in intended management and safety.RESULTS: 208 men with a median baseline PSA of 0.8 ng/mL (range: 0.2-98.4 ng/mL) underwent 18F-DCFPyL-PET/CT. The CLR was 84.8%-87.0% (lower bound of 95% CI: 77.8%-80.4%). 63.9% of evaluable patients had a change in intended management after 18F-DCFPyL-PET/CT. The disease detection rate was 59% to 66% (at least one lesion detected per patient by 18F-DCFPyL-PET/CT by central readers).CONCLUSION: Performance of 18F-DCFPyL-PET/CT achieved the study's primary endpoint, demonstrating disease localization in the setting of negative standard imaging and providing clinically meaningful and actionable information. These data further support the utility of 18F-DCFPyL-PET/CT to localize disease in men with recurrent prostate cancer.

  View details for DOI 10.1158/1078-0432.CCR-20-4573

  View details for PubMedID 33622706

• PSMA-targeted imaging with 18F-DCFPyL-PET/CT in patients (pts) with biochemically recurrent prostate cancer (PCa): A phase III study (CONDOR)-A subanalysis of correct localization rate (CLR) and positive predictive value (PPV) by standard of truth. Pouliot, F., Gorin, M. A., Rowe, S. P., Saperstein, L., Josephson, D., Carroll, P. R., Wong, J. C., Pantel, A. R., Cho, S. Y., Gage, K. L., Piert, M., Iagaru, A., Pollard, J. H., Wong, V., Jensen, J., Stambler, N., Morris, M. J., Siegel, B. A. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.6_suppl.33

  View details for Web of Science ID 000636801500084

• Prognostic value of bone marrow metabolism on pretreatment 18F-FDG PET/CT in patients with metastatic melanoma treated with anti-PD-1 therapy. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Nakamoto, R., Zaba, L. C., Liang, T., Reddy, S. A., Davidzon, G., Aparici, C. M., Nguyen, J., Moradi, F., Iagaru, A., Franc, B. L. 2021

  Abstract

  Purpose: To investigate the prognostic value of 18F-FDG PET/CT parameters in melanoma patients before beginning anti-PD-1 therapy. Methods: Imaging parameters including SUVmax, metabolic tumor volume (MTV), and bone marrow to liver SUVmean ratio (BLR) were measured from baseline PET/CT in 92 patients before the start of anti-PD-1 therapy. Association with survival and imaging parameters combined with clinical factors was evaluated. Clinical and laboratory data between high (> median) and low (≤ median) BLR groups were compared. Results: Multivariate analyses demonstrated that BLR was an independent prognostic factor for PFS and OS (P = 0.017, P = 0.011, respectively). The high BLR group had higher levels of white blood cell count/neutrophil count and C-Reactive Protein than the low BLR group (P < 0.05). Conclusion: Patients with high BLR were associated with poor PFS and OS, potentially explained by evidence of systemic inflammation known to be associated with immunosuppression.

  View details for DOI 10.2967/jnumed.120.254482

  View details for PubMedID 33547210

• A single institution experience with peptide receptor radionuclide therapy (PRRT) in non-midgut neuroendocrine tumors (NETs) Duan, H., Ferri, Fisher, G., Shaheen, S., Davidzon, G., Moradi, F., Nguyen, J., Franc, B., Iagaru, A., Mari, A. C. WILEY. 2021: 181

  View details for Web of Science ID 000620738200168

• A single institution experience with peptide receptor radionuclide therapy (PRRT) in advanced pheochromocytoma and paraganglioma Duan, H., Ferri, Fisher, G., Shaheen, S., Davidzon, G., Moradi, F., Nguyen, J., Franc, B., Iagaru, A., Mari, A. C. WILEY. 2021: 180

  View details for Web of Science ID 000620738200167

• 18F-FDG PET/CT for Evaluation of Post-Transplant Lymphoproliferative Disorder (PTLD). Seminars in nuclear medicine Song, H., Guja, K. E., Iagaru, A. 2021

  Abstract

  Post-transplant lymphoproliferative disorders (PTLD) are a spectrum of heterogeneous lymphoproliferative conditions that are serious and possibly fatal complications after solid organ or allogenic hematopoietic stem cell transplantation. Most PTLD are attributed to Epstein-Barr virus reactivation in B-cells in the setting of immunosuppression after transplantation. Early diagnosis, accurate staging, and timely treatment are of vital importance to reduce morbidity and mortality. Given the often nonspecific clinical presentation and disease heterogeneity of PTLD, tissue biopsy and histopathological analysis are essential to establish diagnosis and most importantly, determine the subtype of PTLD, which guides treatment options. Advanced imaging modalities such as 18F-FDG PET/CT have played an increasingly important role and have shown high sensitivity and specificity in detection, staging, and assessing treatment response in multiple clinical studies over the last two decades. However, larger multicenter prospective validation is still needed to further establish the clinical utility of PET imaging in the management of PTLD. Significantly, new hybrid imaging modalities such as PET/MR may help reduce radiation exposure, which is especially important in pediatric transplant patients.

  View details for DOI 10.1053/j.semnuclmed.2020.12.009

  View details for PubMedID 33455722

• High quality imaging and dosimetry for yttrium-90 (90Y) liver radioembolization using a SiPM-based PET/CT scanner. European journal of nuclear medicine and molecular imaging Duan, H., Khalaf, M. H., Ferri, V., Baratto, L., Srinivas, S. M., Sze, D. Y., Iagaru, A. 2021

  Abstract

  PURPOSE: Transarterial radioembolization (TARE) with yttrium-90 (90Y) microspheres is a liver-directed treatment for primary and secondary hepatic malignancies. Personalized dosimetry aims for maximum treatment effect and reduced toxicity. We aimed to compare pre-treatment voxel-based dosimetry from 99mTc macroaggregated albumin (MAA) SPECT/CT with post-treatment 90Y PET/CT for absorbed dose values, and to evaluate image quality of 90Y SiPM-based PET/CT.METHODS: Forty-two patients (28 men, 14 women, mean age: 67 ± 11 years) with advanced hepatic malignancies were prospectively enrolled. Twenty patients were treated with glass and 22 with resin microspheres. Radiation absorbed doses from planning 99mTc-MAA SPECT/CT and post-therapy 90Y PET/CT were assessed. 90Y PET/CT images were acquired for 20 min and reconstructed to produce 5-, 10-, 15-, and 20-min datasets, then evaluated using the 5-point Likert scale.RESULTS: The mean administered activity was 3.44 ± 1.5 GBq for glass and 1.62 ± 0.7 GBq for resin microspheres. The mean tumor absorbed doses calculated from 99mTc-MAA SPECT/CT and 90Y PET/CT were 175.69 ± 113.76 Gy and 193.58 ± 111.09 Gy (P = 0.61), respectively for glass microspheres; they were 60.18 ± 42.20 Gy and 70.98 ± 49.65 Gy (P = 0.37), respectively for resin microspheres. The mean normal liver absorbed doses from 99mTc-MAA SPECT/CT and 90Y PET/CT were 32.70 ± 22.25 Gy and 30.62 ± 20.09 Gy (P = 0.77), respectively for glass microspheres; they were 18.33 ± 11.08 Gy and 24.32 ± 15.58 Gy (P = 0.17), respectively for resin microspheres. Image quality of 90Y PET/CT at 5-, 10-, 15-, and 20-min scan time showed a Likert score of 3.6 ± 0.54, 4.57 ± 0.58, 4.84 ± 0.37, and 4.9 ± 0.3, respectively.CONCLUSIONS: 99mTc-MAA SPECT/CT demonstrated great accuracy for treatment planning dosimetry. SiPM-based PET/CT scanner showed good image quality at 10-min scan time, acquired in one bed position. A PET/CT scan time of 5 min showed acceptable image quality and suffices for dosimetry and treatment verification. This allows for inclusion of 90Y PET/CT in busy routine clinical workflows. Studies with larger patient cohorts are needed to confirm these findings.

  View details for DOI 10.1007/s00259-021-05188-4

  View details for PubMedID 33443618

• Molecular imaging of pancreatic neoplasms CLINICAL AND TRANSLATIONAL IMAGING Duan, H., Baratto, L., Laudicella, R., Stracuzzi, F., Baldari, S., Iagaru, A. 2021

  View details for DOI 10.1007/s40336-020-00408-7

  View details for Web of Science ID 000607481500001

• The Clinical Utility of 18F-Fluciclovine PET/CT in Biochemically Recurrent Prostate Cancer: an Academic Center Experience Post FDA Approval. Molecular imaging and biology Nakamoto, R. n., Harrison, C. n., Song, H. n., Guja, K. E., Hatami, N. n., Nguyen, J. n., Moradi, F. n., Franc, B. L., Aparici, C. M., Davidzon, G. n., Iagaru, A. n. 2021

  Abstract

  To evaluate the diagnostic performance and clinical utility of 18F-fluciclovine PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC).18F-Fluciclovine scans of 165 consecutive men with BCR after primary definitive treatment with prostatectomy (n = 102) or radiotherapy (n = 63) were retrospectively evaluated. Seventy patients had concurrent imaging with at least one other conventional modality (CT (n = 31), MRI (n = 31), or bone scan (n = 26)). Findings from 18F-fluciclovine PET were compared with those from conventional imaging modalities. The positivity rate and impact of 18F-fluciclovine PET on patient management were recorded. In 33 patients who underwent at least one other PET imaging (18F-NaF PET/CT (n = 12), 68Ga-PSMA11 PET/CT (n = 5), 18F-DCFPyL PET/CT (n = 20), and 68Ga-RM2 PET/MRI (n = 5)), additional findings were evaluated.The overall positivity rate of 18F-fluciclovine PET was 67 %, which, as expected, increased with higher prostate-specific antigen (PSA) levels (ng/ml): 15 % (PSA < 0.5), 50 % (0.5 ≤ PSA < 1), 56 % (1 ≤ PSA < 2), 68 % (2 ≤ PSA < 5), and 94 % (PSA ≥ 5), respectively. One hundred and two patients (62 %) had changes in clinical management based on 18F-fluciclovine PET findings. Twelve of these patients (12 %) had lesion localization on 18F-fluciclovine PET, despite negative conventional imaging. Treatment plans of 14 patients with negative 18F-fluciclovine PET were changed based on additional PET imaging with a different radiopharmaceutical.18F-Fluciclovine PET/CT remains a useful diagnostic tool in the workup of patients with BCR PC, changing clinical management in 62 % of participants in our cohort.

  View details for DOI 10.1007/s11307-021-01583-3

  View details for PubMedID 33469884

• Metastatic and sentinel lymph node mapping using intravenously delivered Panitumumab-IRDye800CW THERANOSTICS Krishnan, G., van den Berg, N. S., Nishio, N., Juniper, G., Pei, J., Zhou, Q., Lu, G., Lee, Y., Ramos, K., Iagaru, A. H., Baik, F. M., Colevas, A. D., Martin, B. A., Rosenthal, E. L. 2021; 11 (15): 7188-7198

  View details for DOI 10.7150/thno.55389

  View details for Web of Science ID 000655136400005

• Disparities in PET Imaging of Prostate Cancer at a Tertiary Academic Medical Center JOURNAL OF NUCLEAR MEDICINE Iagaru, A., Franc, B. 2021; 62 (5): 747-748

  View details for DOI 10.2967/jnumed.121.262029

  View details for Web of Science ID 000755623900036

• Humana and 18F-FDG PET/CT: Another Sequel to the Injustice of Being Judged by the Errors of Others. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Czernin, J. n., Iagaru, A. n. 2021; 62 (1): 1–2

  View details for PubMedID 33334909

• Effect of CD47 Blockade on Vascular Inflammation. The New England journal of medicine Jarr, K. U., Nakamoto, R. n., Doan, B. H., Kojima, Y. n., Weissman, I. L., Advani, R. H., Iagaru, A. n., Leeper, N. J. 2021; 384 (4): 382–83

  View details for DOI 10.1056/NEJMc2029834

  View details for PubMedID 33503349

• Humana and 18F-FDG PET/CT: Another Sequel to the Injustice of Being Judged by the Errors of Others. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Czernin, J., Iagaru, A. 2020

  View details for DOI 10.2967/jnumed.120.260208

  View details for PubMedID 33188152

• OBITUARY Sanjiv "Sam" Gambhir, MD, PhD: In Memoriam (1962-2020) CANCER RESEARCH Wu, A. M., Iagaru, A., Herschman, H., Weissleder, R., Sawyers, C. L. 2020; 80 (20): 4305–6

  View details for DOI 10.1158/0008-5472.CAN-20-2856

  View details for Web of Science ID 000582353000001

• Obituary for Sanjiv Sam Gambhir, MD, PhD. Clinical nuclear medicine Davidzon, G., Franc, B., Mari Aparici, C., Moradi, F., Nguyen, J., Iagaru, A. 2020

  View details for DOI 10.1097/RLU.0000000000003284

  View details for PubMedID 32956118

• Peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors (NET): A single institution experience in the USA Duan, H., Ferri, V., Kunz, P. L., Fisher, G. A., Moradi, F., Davidzon, G. A., Franc, B. L., Iagaru, A. H., Mari, C. SPRINGER. 2020: S468–S469

  View details for Web of Science ID 000577424101134

• The Role of Positron Emission Tomography in Pancreatic Cancer and Gallbladder Cancer. Seminars in nuclear medicine Moradi, F., Iagaru, A. 2020; 50 (5): 434–46

  Abstract

  18F-FDG-PET is complementary to conventional imaging in patients with clinical suspicion for exocrine pancreatic malignancies. It has similar if not superior sensitivity and specificity for detection of cancer, and when combined with contrast enhanced anatomic imaging of the abdomen, can improve diagnostic accuracy and aid in staging, assessment for resectability, radiation therapy planning, and prognostication. Various metabolic pathways affect FDG uptake in pancreatic ductal adenocarcinoma. The degree of uptake reflects histopathology, aggressiveness, metastatic potential, and metabolic profile of malignant cell and their interaction with cancer stroma. After treatment, FDG-PET is useful for detection of residual or recurrent cancer and can be used to assess and monitor response to therapy in unresectable or metastatic disease. The degree and pattern of uptake combined with other imaging features are useful in characterization of incidental pancreatic lesions and benign processes such as inflammation. Several novel PET radiopharmaceuticals have been developed to improve detection and management of pancreatic cancer. Gallbladder carcinoma is typically FDG avid and when anatomic imaging is equivocal PET can be used to assess metastatic involvement with high specificity and inform subsequent management.

  View details for DOI 10.1053/j.semnuclmed.2020.04.002

  View details for PubMedID 32768007

• Prospective Single Institution Study of F18-DCFPyL PET/CT in Biochemically Recurrent Prostate Cancer: An Analysis of Lesions Detection and Localization Iagaru, A., Song, H., Duan, H., Harrison, C., Guja, K., Hatami, N., Franc, B., Nguyen, J., Moradi, F., Mari, C., Davidzon, G. SPRINGER. 2020: S171

  View details for Web of Science ID 000577424100299

• Evaluation of toxicity in peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors (NET) Duan, H., Ferri, V., Kunz, P. L., Fisher, G. A., Moradi, F., Davidzon, G. A., Franc, B. L., Iagaru, A. H., Mari, C. SPRINGER. 2020: S471–S472

  View details for Web of Science ID 000577424101140

• Preliminary Results of F-18-FSPG PET/CT in Patients Referred for Exclusion of Active Cardiac Sarcoidosis after Non-Contributory F-18-FDG PET/CT Iagaru, A., Duan, H., Baratto, L., Gambhir, S. S., Witteles, R. SPRINGER. 2020: S391–S392

  View details for Web of Science ID 000577424100694

• Sanjiv "Sam" Gambhir, MD, PhD 1962-2020 IN MEMORY JOURNAL OF NUCLEAR MEDICINE Iagaru, A., McDougall, I. 2020; 61 (9): 20N–21N

  View details for Web of Science ID 000568832100002

• In Memoriam: Sanjiv "Sam" Gambhir, MD, PhD 1962-2020. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Iagaru, A., McDougall, I. R. 2020; 61 (9): 20N–21N

  View details for PubMedID 32873740

• Imaging Characteristics and Diagnostic Performance of 2-deoxy-2-[18F]fluoro-D-Glucose PET/CT for Melanoma Patients Who Demonstrate Hyperprogressive Disease When Treated with Immunotherapy. Molecular imaging and biology Nakamoto, R., C Zaba, L., Rosenberg, J., Arani Reddy, S., W Nobashi, T., Ferri, V., Davidzon, G., Mari Aparici, C., Nguyen, J., Moradi, F., Iagaru, A., Lewis Franc, B. 2020

  Abstract

  PURPOSE: We investigated the ability of baseline 2-deoxy-2-[18F]fluoro-D-glucose PET/CT parameters, acquired before the start of immunotherapy, to predict development of hyperprogressive disease (HPD) in melanoma patients. We also evaluated the diagnostic performances of ratios of baseline and first restaging PET/CT parameters to diagnose HPD without information of the tumor growth kinetic ratio (TGKR) that requires pre-baseline imaging before baseline imaging (3 timepoint imaging).PROCEDURES: Seventy-six patients who underwent PET/CT before and approximately 3months following initiation of immunotherapy were included. PET/CT parameters, including metabolic tumor volume (MTV) for all melanoma lesions and total measured tumor burden (TMTB) based on irRECIST, were measured from baseline PET/CT (MTVbase and TMTBbase) and first restaging PET/CT (MTVpost and TMTBpost). The ratios of MTV (MTVpost/MTVbase, MTVr) and TMTB (TMTBpost/TMTBbase, TMTBr) were calculated.RESULTS: MTVbase of HPD patients (n=9, TGKR ≥2) was larger than that of non-HPD (n=67, TGKR <2) patients (P<0.05), and HPD patients demonstrated shorter median overall survival (7 vs. more than 60months, P<0.05). The area under the curve (AUC) of MTVbase (≥155.5ml) to predict the risk of HPD was 0.703, with a sensitivity of 66.7% and specificity of 81.2%. The AUCs of MTVr (≥1.25) and TMTBr (≥1.27) to diagnose HPD without information of TGKR were 0.875 and 0.977 with both sensitivities of 100%, and specificities of 79% and 83.9%, respectively.CONCLUSIONS: Patients at high risk of developing HPD could not be accurately identified based on baseline PET/CT parameters. The ratios of baseline and first restaging PET/CT parameters may be helpful to diagnose HPD, when patients do not undergo pre-baseline imaging.

  View details for DOI 10.1007/s11307-020-01526-4

  View details for PubMedID 32789649

• Will FAPI PET/CT Replace FDG PET/CT in the Next Decade?-Counterpoint: No, not so fast! AJR. American journal of roentgenology Moradi, F., Iagaru, A. 2020

  Abstract

  This article does not include an abstract. Please see the accompanying Point by Jeremie Calais and Christine E. Mona.

  View details for DOI 10.2214/AJR.20.23794

  View details for PubMedID 32755204

• PET/MR in neuro-oncology: is it ready for prime-time? CLINICAL AND TRANSLATIONAL IMAGING Laudicella, R., Iagaru, A., Minutoli, F., Gaeta, M., Baldari, S., Bisdas, S. 2020

  View details for DOI 10.1007/s40336-020-00377-x

  View details for Web of Science ID 000543624000001

• Pulmonary Adenocarcinoma Metastasis to the Breast Unexpectedly Discovered on Re-staging 18F-FDG PET/CT in a Woman With a Normal Screening Mammogram. Clinical lung cancer Kozlov, A., Pantel, A., Iagaru, A., Ikeda, D. 2020

  View details for DOI 10.1016/j.cllc.2020.06.012

  View details for PubMedID 32680805

• Prospective evaluation of F-18-DCFPyL PET/CT in biochemically recurrent prostate cancer: Analysis of lesion localization and distribution. Song, H., Duan, H., Harrison, C., Guja, K., Hatami, N., Franc, B., Moradi, F., Aparici, C., Davidzon, G., Srinivas, S., Iagaru, A. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000560368302399

• Impact of PSMA-targeted imaging with 18F-DCFPyL-PET/CT on clinical management of patients (pts) with biochemically recurrent (BCR) prostate cancer (PCa): Results from a phase III, prospective, multicenter study (CONDOR). Morris, M. J., Carroll, P. R., Saperstein, L., Pouliot, F., Josephson, D., Wong, J. C., Pantel, A. R., Cho, S. Y., Gage, K., Piert, M., Iagaru, A., Pollard, J. H., Wong, V., Jensen, J., Stambler, N., Gorin, M. A., Siegel, B. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000560368302346

• A prospective study of Ga-68-RM2 PET/MRI in patients with biochemically recurrent prostate cancer and negative conventional imaging. Baratto, L., Song, H., Duan, H., Aparici, C., Davidzon, G., Moradi, F., Srinivas, S., Iagaru, A. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000560368306300

• High Quality Isotropic Whole-body PET Imaging Using MR Priors Khalighi, M., Deller, T., Spangler-Bickell, M., Wangerin, K., Holley, D., Halbert, K., Zeineh, M., Zaharchuk, G., Mormino, E., Iagaru, A., Moseley, M. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501413

• A pilot study of F-18-FSPG SiPM-based PET/CT in patients referred for exclusion of active cardiac sarcoidosis and negative or non-diagnostic F-18-FDG PET/CT Duan, H., Hatami, N., Baratto, L., Davidzon, G., Aparici, C., Gambhir, S., Koglin, N., Witteles, R., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501539

• Ga-68-RM2 PET/CT in Patients with Newly Diagnosed Intermediate- or High-Risk Prostate Cancer Baratto, L., Duan, H., Hatami, N., Aparici, C., Davidzon, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501196

• Diagnostic Performance of PSMA-Targeted F-18-DCFPyL PET/CT in Men with Biochemically Recurrent Prostate Cancer: Results from the Phase 3, Multicenter CONDOR Study Rowe, S., Gorin, M., Saperstein, L., Pouliot, F., Josephson, D., Carroll, P., Wong, J., Pantel, A., Piert, M., Gage, K., Cho, S., Iagaru, A., Pollard, J., Wong, V., Jensen, J., Stambler, N., Morris, M., Siegel, B. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290500036

• Determining optimal uptake time for Ga-68-labeled radiopharmaceuticals targeting gastrin-releasing peptide receptors with a modified NEMA phantom. Ramos, K., Ferri, V., Baratto, L., Duan, H., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501580

• Ga-68-PSMA-11 PET/MR Imaging before prostatectomy: correlation with surgical pathology and two-year follow up Moradi, F., Baratto, L., Duan, H., Hatami, N., Davidzon, G., Sonn, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290500168

• SUV measurements from images reconstructed with the block sequential regularized expectation maximization algorithm: comparison of motion corrected vs. non-motion corrected data Leonard, Z., Ramos, K., Nguyen, V., Castaneda, P., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501687

• Extrahepatic Ga-68-DOTATATE-Avid Tumor Volume and serum Chromogranin A Predict Short-Term Outcome of Lu-177-DOTATATE in Late-Stage Metastatic Gastroenteropancreatic Neuroendocrine Tumors Song, H., Kunz, P., Franc, B., Moradi, F., Fisher, G., Aparici, C., Iagaru, A., Davidzon, G. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290500275

• PSMA-and GRPR-targeted PET: Preliminary Results in Patients with Biochemically Recurrent Prostate Cancer Baratto, L., Duan, H., Hatami, N., Song, H., Davidzon, G., Franc, B., Aparici, C., Moradi, F., Nguyen, J., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501184

• Prognostic value of volumetric PET parameters at early response evaluation in melanoma patients treated with immunotherapy Nakamoto, R., Zaba, L., Rosenberg, J., Reddy, S., Nobashi, T., Davidzon, G., Aparici, C., Nguyen, J., Moradi, F., Iagaru, A., Franc, B. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290500428

• Imaging characteristics and diagnostic performance of F-18-FDG PET/CT for melanoma patients who demonstrate hyperprogressive disease when treated with immunotherapy Nakamoto, R., Zaba, L., Rosenberg, J., Reddy, S., Nobashi, T., Davidzon, G., Aparici, C., Nguyen, J., Moradi, F., Iagaru, A., Franc, B. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290500424

• Key components of a successful PET/MR department Holley, D., Khalighi, M., Iagaru, A., Gold, G. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501585

• Toxicity identification and evaluation of peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors (NETs) Duan, H., Girod, B., Ninatti, G., Ferri, V., Kunz, P., Fisher, G., Moradi, F., Davidzon, G., Franc, B., Iagaru, A., Aparici, C. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501378

• Peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors (NET): A two-year single institution experience Duan, H., Ninatti, G., Girod, B., Ferri, V., Guja, K., Song, H., Kunz, P., Fisher, G., Iagaru, A., Aparici, C. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501374

• Prognostic values of quantitative and morphological parameters of dbPET in patients with luminal-type breast cancer: A pilot study Miyake, K., Nakamoto, Y., Ikeda, D., Iagaru, A., Daniel, B., Lipson, J., Pal, S., Mittra, E., Guo, H., Kanao, S., Kataoka, M., Toi, M., Togashi, K. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290500482

• INTERIM ANALYSIS RESULTS OF A PROSPECTIVE STUDY OF (68)GA-RM2 PET/MRI IN PATIENTS WITH BIOCHEMICALLY RECURRENT PROSTATE CANCER AND NEGATIVE CONVENTIONAL IMAGING Baratto, L., Song, H., Duan, H., Aparici, C., Hatami, N., Davidzon, G., Moradi, F., Iagaru, A. LIPPINCOTT WILLIAMS & WILKINS. 2020: E1118

  View details for Web of Science ID 000527010300463

• Fungal endocarditis resembling primary cardiac malignancy in a patient with B-cell ALL with culture confirmation. Radiology case reports Girod, B. J., Guja, K. E., Davidzon, G., Chan, F., Zucker, E., Franc, B. L., Moradi, F., Iagaru, A., Aparici, C. M. 2020; 15 (2): 117–19

  Abstract

  Fungal endocarditis is a rare subtype of infective endocarditis that often presents with nonspecific symptoms in patients with complex medical histories, making diagnosis challenging. Patients with a history of ALL may present with congestive heart failure, chemo-induced cardiomyopathy, acute coronary syndrome, cardiac lymphomatous metastasis, or infections. We present the case of a patient with a history of ALL who presented with acute coronary syndrome and imaging concerning for primary cardiac lymphoma, when in fact the patient ended up suffering from culture proven fungal endocarditis.

  View details for DOI 10.1016/j.radcr.2019.10.022

  View details for PubMedID 31768196

• Single institution experience with peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET) Duan, H., Ninatti, G., Girod, B., Ferri, V., Kunz, P. L., Fisher, G. A., Moradi, F., Davidzon, G., Franc, B., Iagaru, A., Mari, C. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000530922700601

• Response to: Letter to the Editors: Re: Simultaneous PET/MRI in the Evaluation of Breast and Prostate Cancer Using Combined Na[18F]F and [18F]FDG: A Focus on Skeletal Lesions. Molecular imaging and biology Sonni, I., Minamimoto, R., Baratto, L., Iagaru, A. 2020

  View details for DOI 10.1007/s11307-020-01471-2

  View details for PubMedID 31933023

• Letter to the Editor: "Disparities in PET imaging for prostate cancer at a tertiary academic medical center". Journal of nuclear medicine : official publication, Society of Nuclear Medicine Franc, B. L., Iagaru, A. n. 2020

  View details for DOI 10.2967/jnumed.120.258160

  View details for PubMedID 33127623

• Sanjiv Sam Gambhir obituary for EJNMMI. European journal of nuclear medicine and molecular imaging Iagaru, A. n., McDougall, I. R. 2020

  View details for DOI 10.1007/s00259-020-04987-5

  View details for PubMedID 32761365

• The Effect of Various β Values on Image Quality and Semiquantitative Measurements in 68Ga-RM2 and 68Ga-PSMA-11 PET/MRI Images Reconstructed With a Block Sequential Regularized Expectation Maximization Algorithm. Clinical nuclear medicine Baratto, L. n., Duan, H. n., Ferri, V. n., Khalighi, M. n., Iagaru, A. n. 2020

  Abstract

  To compare the block sequential regularized expectation maximization (BSREM) algorithm with the ordered subsets expectation maximization (OSEM) algorithm and to evaluate how different penalty factors (b values) influence image quality and SUV measurements.We analyzed data from 78 prostate cancer patients who underwent Ga-RM2 (n = 42) or Ga-prostate-specific membrane antigen (PSMA)-11 (n = 36) PET/MRI. The raw PET data were retrospectively reconstructed using both time-of-flight (TOF)-BSREM with b values of 250, 350, 500, 750, and 1000 and TOF-OSEM. Each reconstruction was reviewed independently by 3 nuclear medicine physicians and scored qualitatively using a Likert scale (1 = poor, 5 = excellent quality). SUV measurements were analyzed as well.Fifty-seven lesions were detected (21 on Ga-RM2 and 36 on Ga-PSMA-11 PET/MRI); SUVmax decreased with the increase of β values for both tracers. Background noise (SUVsd) decreased with increasing of β values for both tracers. The mean ± SD scores for Ga-RM2 PET images were 2.4 ± 0.5 for b = 250 reconstructions, 3.2 ± 0.6 for b = 350, 4 ± 0.6 for b = 500, 4.5 ± 0.5 for b = 750, 4.4 ± 0.7 for b = 1000, and 3.4 ± 0.6 for TOF-OSEM. The mean ± SD scores for Ga-PSMA-11 PET images were 3.2 ± 0.8 for b = 250 reconstructions, 4.1 ± 0.8 for b = 350, 4.7 ± 0.6 for b = 500, 4.8 ± 0.4 for b = 750, 4.7 ± 0.6 for b = 1000, and 3.8 ± 0.5 for TOF-OSEM.Time-of-flight-BSREM algorithm improves image quality. Different b values should be used for different Ga-labeled radiopharmaceuticals such as those targeting GRPR and PSMA receptors. Once selected, the same b value should be consistently used because SUVmax measurements differ with different b values.

  View details for DOI 10.1097/RLU.0000000000003075

  View details for PubMedID 32433170

• Human biodistribution and radiation dosimetry of [18F]DASA-23, a PET probe targeting pyruvate kinase M2. European journal of nuclear medicine and molecular imaging Beinat, C. n., Patel, C. B., Haywood, T. n., Shen, B. n., Naya, L. n., Gandhi, H. n., Holley, D. n., Khalighi, M. n., Iagaru, A. n., Davidzon, G. n., Gambhir, S. S. 2020

  Abstract

  To assess the safety, biodistribution, and radiation dosimetry of the novel positron emission tomography (PET) radiopharmaceutical 1-((2-fluoro-6-[[18F]]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in healthy volunteers.We recruited 5 healthy volunteers who provided a written informed consent. Volunteers were injected with 295.0 ± 8.2 MBq of [18F]DASA-23 intravenously. Immediately following injection, a dynamic scan of the brain was acquired for 15 min. This was followed by serial whole-body PET/MRI scans acquired up to 3 h post-injection. Blood samples were collected at regular intervals, and vital signs monitored pre- and post-radiotracer administration. Regions of interest were drawn around multiple organs, time-activity curves were calculated, and organ uptake and dosimetry were estimated with OLINDA/EXM (version 1.1) software.All subjects tolerated the PET/MRI examination, without adverse reactions to [18F]DASA-23. [18F]DASA-23 passively crossed the blood-brain barrier, followed by rapid clearance from the brain. High accumulation of [18F]DASA-23 was noted in organs such as the gallbladder, liver, small intestine, and urinary bladder, suggesting hepatobiliary and urinary clearance. The effective dose of [18F]DASA-23 was 23.5 ± 5.8 μSv/MBq.We successfully completed a pilot first-in-human study of [18F]DASA-23. Our results indicate that [18F]DASA-23 can be used safely in humans to evaluate pyruvate kinase M2 levels. Ongoing studies are evaluating the ability of [18F]DASA-23 to visualize intracranial malignancies, NCT03539731.ClinicalTrials.gov, NCT03539731 (registered 28 May 2018).

  View details for DOI 10.1007/s00259-020-04687-0

  View details for PubMedID 31938892

• Shifting Trends and Informed Decision Making in the Management of Graves' Disease. Thyroid : official journal of the American Thyroid Association Seib, C. D., Chen, J. n., Iagaru, A. n. 2020

  Abstract

  Not applicable for invited commentary.

  View details for DOI 10.1089/thy.2020.0114

  View details for PubMedID 32046610

• ACR Stakeholder Prostate Summit. Journal of the American College of Radiology : JACR Weinreb, J. n., Choyke, P. n., Iagaru, A. n., Ippolito, J. n., Lockhart, M. n., Merrick, G. n., Sachdev, S. n., Silva, E. n., Taneja, S. S., Tempany, C. n., Wahl, R. n., Rosenkrantz, A. n. 2020

  View details for DOI 10.1016/j.jacr.2020.03.031

  View details for PubMedID 32360452

• Visualization of diagnostic and therapeutic targets in glioma with molecular imaging Frontiers in Immunology Li, D., Patel, C. B., Xu, G., Iagaru, A., Zhu, Z., Zhang, L., Cheng, Z. 2020

  View details for DOI 10.3389/fimmu.2020.592389

• Sanjiv Sam Gambhir (November 23, 1962-July 18, 2020). Molecular imaging and biology James, M. n., Iagaru, A. n. 2020

  View details for DOI 10.1007/s11307-020-01528-2

  View details for PubMedID 32797347

• Two Patient Studies of a Companion Diagnostic Immuno-Positron Emission Tomography (PET) Tracer for Measuring Human CA6 Expression in Cancer for Antibody Drug Conjugate (ADC) Therapy. Molecular imaging Natarajan, A., Srinivas, S. M., Azevedo, C., Greene, L., Bauchet, A., Jouannot, E., Lacoste-Bourgeacq, A., Guizon, I., Cohen, P., Naneix, A., Ilovich, O., Cisneros, J., Rupanarayan, K., Chin, F. T., Iagaru, A., Dirbas, F. M., Karam, A., Gambhir, S. S. 2020; 19: 1536012120939398

  Abstract

  An antigen binding fragment (BFab) derived from a tumor-associated mucin 1-sialoglycotope antigen (CA6) targeting antibody (huDS6) was engineered. We synthesized a companion diagnostic positron emission tomography (PET) tracer by radiolabeling BFab with [64Cu] to measure CA6 expression on cancer tissues prior to anti-human CA6 (huDS6-DM4 antibody-drug conjugate) therapy for ovarian and breast cancer patients. After chemotherapy, the ovarian patient received PET scan with 18F-2-fluoro-2-deoxyglucose ([18F]FDG: 10 mCi), followed by [64Cu]-DOTA-BFab ([64Cu]BFab; 5.5 mCi) 1 week later for PET scanning of CA6 expression and subsequent surgery. The breast cancer patient was treated with chemotherapy before primary tumor resection and subsequent [18F]FDG-PET scan. 4 weeks later the patient received of [64Cu]BFab (11.7 mCi) for CA6 PET scan. Whole body [18F]FDG-PET of the breast cancer patient indicated FDG-avid tumor metastases to the liver, bilateral hila and thoracic spine, but no uptake was observed for the ovarian patient. Each patient was also imaged by PET/CT with [64Cu]BFab at 1 and 24 hours after tracer administration. The [64Cu]BFab tracer was well tolerated by both patients without adverse effects, and no significant tracer uptake was observed in both patients. Immunohistochemistry (IHC) data indicated CA6 expressions were weak to intermediate and matched with the [64Cu]BFab-PET signals.

  View details for DOI 10.1177/1536012120939398

  View details for PubMedID 33104454

• Deep learning detection of prostate cancer recurrence with 18F-FACBC (fluciclovine, Axumin®) positron emission tomography. European journal of nuclear medicine and molecular imaging Lee, J. J., Yang, H. n., Franc, B. L., Iagaru, A. n., Davidzon, G. A. 2020

  Abstract

  To evaluate the performance of deep learning (DL) classifiers in discriminating normal and abnormal 18F-FACBC (fluciclovine, Axumin®) PET scans based on the presence of tumor recurrence and/or metastases in patients with prostate cancer (PC) and biochemical recurrence (BCR).A total of 251 consecutive 18F-fluciclovine PET scans were acquired between September 2017 and June 2019 in 233 PC patients with BCR (18 patients had 2 scans). PET images were labeled as normal or abnormal using clinical reports as the ground truth. Convolutional neural network (CNN) models were trained using two different architectures, a 2D-CNN (ResNet-50) using single slices (slice-based approach) and the same 2D-CNN and a 3D-CNN (ResNet-14) using a hundred slices per PET image (case-based approach). Models' performances were evaluated on independent test datasets.For the 2D-CNN slice-based approach, 6800 and 536 slices were used for training and test datasets, respectively. The sensitivity and specificity of this model were 90.7% and 95.1%, and the area under the curve (AUC) of receiver operating characteristic curve was 0.971 (p < 0.001). For the case-based approaches using both 2D-CNN and 3D-CNN architectures, a training dataset of 100 images and a test dataset of 28 images were randomly allocated. The sensitivity, specificity, and AUC to discriminate abnormal images by the 2D-CNN and 3D-CNN case-based approaches were 85.7%, 71.4%, and 0.750 (p = 0.013) and 71.4%, 71.4%, and 0.699 (p = 0.053), respectively.DL accurately classifies abnormal 18F-fluciclovine PET images of the pelvis in patients with BCR of PC. A DL classifier using single slice prediction had superior performance over case-based prediction.

  View details for DOI 10.1007/s00259-020-04912-w

  View details for PubMedID 32556481

• Imaging the Distribution of Gastrin Releasing Peptide Receptors in Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Baratto, L. n., Duan, H. n., Maecke, H. R., Iagaru, A. n. 2020

  Abstract

  Targeting tumor-expressed receptors using selective molecules for diagnostic, therapeutic or both diagnostic and therapeutic (theragnostic) purposes is a promising approach in oncological applications. Such approaches have increased significantly over the past decade. Peptides such as gastrin-releasing peptide receptors (GRPR) targeting radiopharmaceuticals are small molecules with fast blood clearance and urinary excretion. They demonstrate good tissue diffusion, low immunogenicity, and highly selective binding to their target cell-surface receptors. They are also easily produced. GRPR, part of the bombesin (BBN) family, are overexpressed in many tumors, including breast and prostate cancer, and therefore represent an attractive target for future development.

  View details for DOI 10.2967/jnumed.119.234971

  View details for PubMedID 32060215

• Clinical application of Fluciclovine PET, choline PET and gastrin-releasing polypeptide receptor (bombesin) targeting PET in prostate cancer. Current opinion in urology Ceci, F. n., Castellucci, P. n., Polverari, G. n., Iagaru, A. n. 2020

  Abstract

  The aim of this review is to explore the clinical application of different PET radiopharmaceuticals in prostate cancer (PCa), beyond inhibitors of the prostate-specific membrane antigen (PSMA).Choline PET represented in the last decades the standard of reference for PET imaging in PCa and has been recently included in clinical trials evaluating the efficacy of metastasis-directed therapy in oligo-metastatic disease. Fluciclovine, as synthetic amino acid, has been proposed for investigating PCa. The results obtained by the first prospective studies led to FDA approval in 2016 in patients with biochemical recurrence. Recently, phase II/III trials explored its accuracy compared with PSMA PET and its impact on patient management. Imaging the gastrin-releasing polypeptide receptor (GRPR) recently drawn attention. Radio-labelled GRPR antagonists have the potential to be used as theranostic agents. Further evaluation is needed to understand the relation between GRPR expression and hormonal-resistant PCa, and for tumors characterized by heterogeneity of receptors expressed (e.g. PSMA-negative) on their cell surface.Other new generation PET tracers may play an important role in PCa, namely in case of PSMA-negative phenotypes.

  View details for DOI 10.1097/MOU.0000000000000794

  View details for PubMedID 32701717

• An unusual presentation of recurrent T cell lymphoma: angiocentric pattern of cutaneous uptake on [18F]FDG PET/CT. European journal of nuclear medicine and molecular imaging Guja, K. E., Brown, R. n., Girod, B. n., Song, H. n., Harrison, C. n., Franc, B. L., Moradi, F. n., Davidzon, G. n., Iagaru, A. n., Aparici, C. M. 2020

  View details for DOI 10.1007/s00259-020-05026-z

  View details for PubMedID 32918110

• Prognostic value of volumetric PET parameters at early response evaluation in melanoma patients treated with immunotherapy. European journal of nuclear medicine and molecular imaging Nakamoto, R. n., Zaba, L. C., Rosenberg, J. n., Reddy, S. A., Nobashi, T. W., Davidzon, G. n., Aparici, C. M., Nguyen, J. n., Moradi, F. n., Iagaru, A. n., Franc, B. L. 2020

  Abstract

  The purpose of this study was to investigate the prognostic value of whole-body metabolic tumor volume (MTV) and other metabolic tumor parameters, obtained from baseline and first restaging 18F-FDG PET/CT scans in melanoma patients treated with immune checkpoint inhibitors (ICIs).Eighty-five consecutive melanoma patients (M, 57; F, 28) treated with ICIs who underwent PET/CT scans before and approximately 3 months after the start of immunotherapy were retrospectively enrolled. Metabolic tumor parameters including MTV for all melanoma lesions were measured on each scan. A Cox proportional hazards model was used for univariate and multivariate analyses of metabolic parameters combined with known clinical prognostic factors associated with overall survival (OS). Kaplan-Meier curves for patients dichotomized based on median values of imaging parameters were generated.The median OS time in all patients was 45 months (95% CI 24-45 months). Univariate analysis demonstrated that MTV obtained from first restaging PET/CT scans (MTVpost) was the strongest prognostic factor for OS among PET/CT parameters (P < 0.0001). The median OS in patients with high MTVpost (≥ 23.44) was 16 months (95% CI 12-32 months) as compared with more than 60 months in patients with low MTVpost (< 23.44) (P = 0.0003). A multivariate model including PET/CT parameters and known clinical prognostic factors revealed that MTVpost and the presence of central nervous system lesions were independent prognostic factors for OS (P = 0.0004, 0.0167, respectively). One pseudoprogression case (1.2%) was seen in this population and classified into the high MTVpost group.Whole-body metabolic tumor volume from PET scan acquired approximately 3 months following initiation of immunotherapy (MTVpost) is a strong prognostic indicator of OS in melanoma patients. Although the possibility of pseudoprogression must be considered whenever evaluating first restaging PET imaging, it only occurred in 1 patient in our cohort.

  View details for DOI 10.1007/s00259-020-04792-0

  View details for PubMedID 32296882

• Prospective Evaluation in an Academic Center of 18F-DCFPyL PET/CT in Biochemically Recurrent Prostate Cancer: A Focus on Localizing Disease and Changes in Management. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Song, H., Harrison, C., Duan, H., Guja, K., Hatami, N., Franc, B., Moradi, F., Mari Aparici, C., Davidzon, G., Iagaru, A. 2019

  Abstract

  18F-DCFPyL is a promising PET radiopharmaceutical targeting prostate specific membrane antigen (PSMA). We present our experience in this single academic center prospective study evaluating the positivity rate of 18F-DCFPyL PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC). Methods: We prospectively enrolled 72 men (52-91 years old, mean±SD: 71.5±7.2) with BCR after primary definitive treatment with prostatectomy (n = 42) or radiotherapy (n = 30). The presence of lesions compatible with PC was evaluated by two independent readers. Fifty-nine patients had concurrent scans with at least one other conventional scan: bone scan (24), CT (21), MR (20), 18F-Fluciclovine PET/CT (18) and/or 18F-NaF PET (14). Findings from 18F-DCFPyL PET/CT were compared with those from other modalities. Impact on patient management based on 18F-DCFPyL PET/CT was recorded from clinical chart review. Results: 18F-DCFPyL PET/CT had an overall positivity rate of 85%, which increased with higher prostate specific antigen (PSA) levels (ng/mL): 50% (PSA<0.5), 69% (0.5≤PSA<1), 100% (1≤PSA<2), 91% (2≤PSA<5) and 96% (PSA≥5), respectively. 18F-DCFPyL PET detected more lesions than conventional imaging. For anatomic imaging, 20/41 (49%) CT/MRI had congruent findings with 18F-DCFPyL, while 18F-DCFPyL PET was positive in 17/41 (41%) cases with negative CT/MRI. For bone imaging, 26/38 (68%) bone scan/18F-NaF PET were congruent with 18F-DCFPyL PET, while 18F-DCFPyL PET localized bone lesions in 8/38 (21%) patients with negative bone scan/18F-NaF PET. In 8/18 (44%) patients, 18F-Fluciclovine PET had located the same lesions as the 18F-DCFPyL PET, while 5/18 (28%) patients with negative 18F-Fluciclovine had positive 18F-DCFPyL PET findings and 1/18 (6%) patient with negative 18F-DCFPyL had uptake in the prostate bed on 18F-Fluciclovine PET. In the remaining 4/18 (22%) patients, 18F-DCFPyL and 18F-Fluciclovine scans showed different lesions. Lastly, 43/72 (60%) patients had treatment changes after 18F-DCFPyL PET and, most noticeably, 17 of these patients (24% total) had lesion localization only on 18F-DCFPyL PET, despite negative conventional imaging. Conclusion: 18F-DCFPyL PET/CT is a promising diagnostic tool in the work-up of biochemically recurrent prostate cancer given the high positivity rate as compared to FDA-approved currently available imaging modalities and its impact on clinical management in 60% of patients.

  View details for DOI 10.2967/jnumed.119.231654

  View details for PubMedID 31628216

• Evaluation of integrin alphavbeta6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis. Nature communications Kimura, R. H., Wang, L., Shen, B., Huo, L., Tummers, W., Filipp, F. V., Guo, H. H., Haywood, T., Abou-Elkacem, L., Baratto, L., Habte, F., Devulapally, R., Witney, T. H., Cheng, Y., Tikole, S., Chakraborti, S., Nix, J., Bonagura, C. A., Hatami, N., Mooney, J. J., Desai, T., Turner, S., Gaster, R. S., Otte, A., Visser, B. C., Poultsides, G. A., Norton, J., Park, W., Stolowitz, M., Lau, K., Yang, E., Natarajan, A., Ilovich, O., Srinivas, S., Srinivasan, A., Paulmurugan, R., Willmann, J., Chin, F. T., Cheng, Z., Iagaru, A., Li, F., Gambhir, S. S. 2019; 10 (1): 4673

  Abstract

  Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin alphavbeta6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer's safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin alphavbeta6.

  View details for DOI 10.1038/s41467-019-11863-w

  View details for PubMedID 31611594

• Malignant cutaneous melanoma:updates inPET imaging. Current radiopharmaceuticals Laudicella, R., Baratto, L., Minutoli, F., Baldari, S., Iagaru, A. 2019

  Abstract

  BACKGROUND: Cutaneous malignant melanoma is a neoplasm whose incidence and mortality are dramatically increasing. 18F-FDG PET/CT gained clinical acceptance over the past 2 decades in the evaluation of several glucose-avid neoplasms, including malignant melanoma, particularly for the assessment for distant metastases, recurrence and response to therapy.OBJECTIVE: To describe the advancements of nuclear medicine for imaging melanoma with particular attention to 18F-FDG-PET, and its current state-of-the-art technical innovations.METHODS: A comprehensive search strategy was used based on SCOPUS and PubMed databases. From all studies published in English, we selected the articles that evaluated the technological insights of 18F-FDG-PET in the assessment of melanoma.RESULTS: State-of-the-art silicon photomultipliers based detectors ("digital") PET/CT scanners are nowadays more common, showing technical innovations that may have beneficial implications for patients with melanoma. Steady improvements in detectors design and architecture, as well as the implementation of both software and hardware technology (i.e., TOF, point spread function, etc.), resulted in significant improvements in PET image quality while reducing radiotracer dose and scanning time.CONCLUSION: Recently introduced digital PET detector technology in PET/CT and PET/MRI yields higher intrinsic system sensitivity compared with the latest generation analog technology, enabling the detection of very small lesions with potential impact on disease outcome.

  View details for DOI 10.2174/1874471012666191015095550

  View details for PubMedID 31749439

• Multimodality Hyperpolarized C-13 MRS/PET/Multiparametric MR Imaging for Detection and Image-Guided Biopsy of Prostate Cancer: First Experience in a Canine Prostate Cancer Model MOLECULAR IMAGING AND BIOLOGY Bachawal, S. V., Park, J., Valluru, K. S., Loft, M., Felt, S. A., Vilches-Moure, J. G., Saenz, Y. F., Daniel, B., Iagaru, A., Sonn, G., Cheng, Z., Spielman, D. M., Willmann, J. K. 2019; 21 (5): 861–70

  View details for DOI 10.1007/s11307-018-1235-6

  View details for Web of Science ID 000483788100009

• Prospective evaluation of F-18-DCFPyL in Patients with Biochemically Recurrent Prostate Cancer Iagaru, A., Duan, H., Song, H., Harrison, C., Guja, K., Franc, B., Moradi, F., Davidzon, G. SPRINGER. 2019: S593

  View details for Web of Science ID 000492444405132

• Machine Learning to Detect Prostate Cancer Recurrence using F-18-Fluciclovine PET Davidzon, G. A., Lee, J., Yang, H., Song, H., Harrison, C., Iagaru, A. SPRINGER. 2019: S65–S66

  View details for Web of Science ID 000492444400097

• Ga-68-RM2 PET/CT in Patients with Newly Diagnosed Intermediate- or High-Risk Prostate Cancer Iagaru, A., Baratto, L., Duan, H., Hatami, N., Mari, C., Davidzon, G. SPRINGER. 2019: S277–S278

  View details for Web of Science ID 000492444402125

• Physiological Ga-68-RM2 Uptake in Patients with Biochemically Recurrent Prostate Cancer: An Atlas of Semi-Quantitative Measurements Baratto, L., Duan, H., Laudicella, R., Ferri, V., Toriihara, A., Hatami, N., Iagaru, A. SPRINGER. 2019: S606–S607

  View details for Web of Science ID 000492444405162

• Clinical Follow-up after Imaging and Dosimetry for Yttrium-90 (Y-90) Liver Radioembolization Using a SiPM-based PET/CT Scanner Duan, H., Khalaf, M. H., Baratto, L., Srinivas, S., Sze, D., Iagaru, A. SPRINGER. 2019: S259

  View details for Web of Science ID 000492444402089

• The Effect of Different Time Per Bed Position on Image Quality and Semi-Quantitative Measurements in Ga-68-RM2 and Ga-68-PSMA11 PET/MR Images Baratto, L., Duan, H., Gandhi, H., Khalighi, M., Iagaru, A. SPRINGER. 2019: S783

  View details for Web of Science ID 000492444407094

• Physiological 68Ga-RM2 uptake in patients with biochemically recurrent prostate cancer: an atlas of semi-quantitative measurements. European journal of nuclear medicine and molecular imaging Baratto, L., Duan, H., Laudicella, R., Toriihara, A., Hatami, N., Ferri, V., Iagaru, A. 2019

  Abstract

  AIM: 68Ga-RM2 is a bombesin (BBN) analog that targets the gastrin releasing peptide receptors (GRPR) overexpressed in many cancer cells, including prostate cancer (PC). It has been reported to successfully detect primary and recurrent PC. Here, we describe the distribution and range of physiological uptake of 68Ga-RM2 in 95 patients with biochemically recurrent (BCR) PC.MATERIALS AND METHODS: Ninety-five participants had simultaneous PET/MRI for BCR PC and were prospectively enrolled in this study. Maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) were measured in 24 normal anatomical structures for each participant. Three readers evaluated the images independently. Uptake in various normal tissues was classified into 4 different categories: no significant uptake if SUVmean was less than SUVmean of the aortic arch (AA); mild if SUVmean was less or equal to 2.5, but higher than SUVmean of the AA; moderate if SUVmean was higher than 2.5, but less or equal to 5; intense if SUVmean was higher than 5.RESULTS: The most intense uptake was observed in the urinary bladder, due to excretion of the radiotracer. No significant uptake was seen in the brain, salivary glands, lungs, myocardium, skeleton, muscles, and fat. Liver, spleen, and adrenal glands had mostly no significant uptake; the gastrointestinal tract had intense physiological uptake, with pancreas being the organ with the highest SUVmax measurements (average SUVmax 64.91). Mild and moderate uptake was measured in the esophagus (average SUVmax 3.99), while the stomach wall, duodenum, and rectum had mild uptake (average SUVmax 2.49, 3.42, and 3.58, respectively).CONCLUSIONS: 68Ga-RM2 has been mostly evaluated for PC detection, but it can be used for other tumors overexpressing GRPR such as breast cancer. This atlas of normal biodistribution and SUV measurements in healthy tissues will help physicians distinguish between physiological vs. pathological uptake, as well as potentially assist with planning future studies using GRPR targeting radiopharmaceuticals.

  View details for DOI 10.1007/s00259-019-04503-4

  View details for PubMedID 31478089

• Improved Scatter Correction to Eliminate Halo Artifacts for Ga-68-Labeled Radiopharmaceuticals in PET Imaging JOURNAL OF NUCLEAR MEDICINE Wangerin, K., Iagaru, A. 2019; 60 (9): 1334

  View details for DOI 10.2967/jnumed.119.230557

  View details for Web of Science ID 000484372100029

• Treatment and outcomes in classic Hodgkin lymphoma post-transplant lymphoproliferative disorder in children PEDIATRIC BLOOD & CANCER Twist, C. J., Hiniker, S. M., Gratzinger, D., Gutkin, P. M., Merriott, D. J., Iagaru, A., Link, M. P., Donaldson, S. S. 2019; 66 (8)

  View details for DOI 10.1002/pbc.27803

  View details for Web of Science ID 000472549200013

• 18F-FDG PET/MR Refines Evaluation in Newly Diagnosed Metastatic Urethral Adenocarcinoma. Nuclear medicine and molecular imaging Laudicella, R., Davidzon, G., Vasanawala, S., Baldari, S., Iagaru, A. 2019; 53 (4): 296-299

  Abstract

  We described the clinical impact of 18F-FDG PET/MR in refining the evaluation of a 39-year-old female with newly diagnosed metastatic urethral adenocarcinoma. We detailed the diagnostic imaging workup focusing our attention on the CT, MR, and 18F-FDG PET/MR different findings. In this case, 18F-FDG PET/MR imaging evaluation resulted not only effective but also altered staging and spared additional invasive procedures in the assessment of a metastatic urethral adenocarcinoma. Combining a highly sensitive PET with the increase tissue resolution of MR (PET/MR) may improve abdominal and pelvic lesion detection outperforming PET/CT for this indication.

  View details for DOI 10.1007/s13139-019-00597-8

  View details for PubMedID 31456863

  View details for PubMedCentralID PMC6694445

• Tumor Drug Penetration Measurements Could Be the Neglected Piece of the Personalized Cancer Treatment Puzzle CLINICAL PHARMACOLOGY & THERAPEUTICS Bartelink, I. H., Jones, E. F., Shahidi-Latham, S. K., Lee, P., Zheng, Y., Vicini, P., van't Veer, L., Wolf, D., Iagaru, A., Kroetz, D. L., Prideaux, B., Cilliers, C., Thurber, G. M., Wimana, Z., Gebhart, G. 2019; 106 (1): 148–63

  Abstract

  Precision medicine aims to use patient genomic, epigenomic, specific drug dose, and other data to define disease patterns that may potentially lead to an improved treatment outcome. Personalized dosing regimens based on tumor drug penetration can play a critical role in this approach. State-of-the-art techniques to measure tumor drug penetration focus on systemic exposure, tissue penetration, cellular or molecular engagement, and expression of pharmacological activity. Using in silico methods, this information can be integrated to bridge the gap between the therapeutic regimen and the pharmacological link with clinical outcome. These methodologies are described, and challenges ahead are discussed. Supported by many examples, this review shows how the combination of these techniques provides enhanced patient-specific information on drug accessibility at the tumor tissue level, target binding, and downstream pharmacology. Our vision of how to apply tumor drug penetration measurements offers a roadmap for the clinical implementation of precision dosing.

  View details for DOI 10.1002/cpt.1211

  View details for Web of Science ID 000474029300031

  View details for PubMedID 30107040

  View details for PubMedCentralID PMC6617978

• F-18-FPPRGD(2) PET/CT in patients with metastatic renal cell cancer EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Toriihara, A., Duan, H., Thompson, H. M., Park, S., Hatami, N., Baratto, L., Fan, A. C., Iagaru, A. 2019; 46 (7): 1518–23

  View details for DOI 10.1007/s00259-019-04295-7

  View details for Web of Science ID 000468983000017

• Simultaneous PET/MRI in the Evaluation of Breast and Prostate Cancer Using Combined Na[18F] F and [18F]FDG: a Focus on Skeletal Lesions. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Sonni, I., Minamimoto, R., Baratto, L., Gambhir, S. S., Loening, A. M., Vasanawala, S. S., Iagaru, A. 2019

  Abstract

  PURPOSE: The purpose of this study is to prospectively evaluate the performance of sodium 18F]fluoride (Na[18F]F)/2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) simultaneous time-of-flight enabled positron emission tomography (PET)/magnetic resonance imaging (MRI) for the detection of skeletal metastases in selected patients with advanced breast and prostate cancers.PROCEDURE: The institutional review board approved this HIPAA-compliant protocol. Written informed consent was obtained from each patient. A total of 74 patients (23 women and 51 men with breast and prostate cancer, respectively) referred for standard-of-care whole-body bone scintigraphy (WBBS) were enrolled in this prospective study. All patients underwent a [99mTc]methyldiphosphonate ([99mTc]MDP) WBBS followed by Na[18F]F/[18F]FDG PET/MRI. Lesions detected by each imaging modality were tabulated and a lesion-based and patient-based analysis was conducted.RESULTS: On a patient-based analysis, [99mTc]MDP WBBS identified skeletal lesions in 37 patients and PET/MRI in 45 patients. On a lesion-based analysis, WBBS identified a total of 81 skeletal lesions, whereas PET/MRI identified 140 lesions. Additionally, PET/MRI showed extra-skeletal lesions in 19 patients, including lymph nodes (16), prostate (4) lung (3), and liver (2) lesions.CONCLUSIONS: The ability of Na[18F]F/[18F]FDG PET/MRI to identify more skeletal lesions than 99mTc-MDP WBBS and to additionally identify extra-skeletal disease may be beneficial for patient care and represent an alternative to the single modalities performed separately. Na[18F]F/[18F]FDG PET/MRI is a promising approach for evaluation of skeletal and extra-skeletal lesions in a selected population of breast and prostate cancer patients.

  View details for DOI 10.1007/s11307-019-01392-9

  View details for PubMedID 31236756

• State of the Art PET/MRI: Applications and Limitations - Summary of the First ISMRM/SNMMI Co-Provided Workshop on PET/MRI. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Hope, T. A., Fayad, Z. A., Fowler, K. J., Holley, D., Iagaru, A. H., McMillan, A., Veit-Haibach, P., Witte, R. J., Zaharchuk, G., Catana, C. 2019

  Abstract

  Since the introduction of simultaneous PET/MRI in 2011, there have been significant advancements. In this review, we highlight a number of the technical advancements that have been made primarily in attenuation correction and motion correction. Additionally, we review the status of multiple clinical applications using PET/MRI. This review was based on the experiences at the first ISMRM/SNMMI co-sponsored PET/MRI conference.

  View details for DOI 10.2967/jnumed.119.227231

  View details for PubMedID 31123099

• Treatment and outcomes in classic Hodgkin lymphoma post-transplant lymphoproliferative disorder in children. Pediatric blood & cancer Twist, C. J., Hiniker, S. M., Gratzinger, D., Gutkin, P. M., Merriott, D. J., Iagaru, A., Link, M. P., Donaldson, S. S. 2019: e27803

  Abstract

  Classic Hodgkin lymphoma post-transplant lymphoproliferative disorder (HL-PTLD) has been rarely reported in children, with limited data available to guide treatment decisions. We report a retrospective review of five children diagnosed with classic HL-PTLD following solid organ transplant between 2007 and 2013 at Stanford University. Patients were treated with Stanford V chemotherapy and involved field radiation therapy. With a median follow-up of 7.2 years (range, 4.7-10.5 years) since diagnosis, all patients remain in remission from HL-PTLD and free from graft failure. In this series, combined modality therapy with risk-adapted chemotherapy and radiation therapy was a successful strategy for the treatment of classic HL-PTLD.

  View details for PubMedID 31062898

• Prospective Evaluation of F-18-DCFPyL PET/CT and Conventional Imaging in Patients with Biochemically Recurrent Prostate Cancer Song, H., Harrison, C., Guja, K., Franc, B., Moradi, F., Davidzon, G., Aparici, C., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2019

  View details for Web of Science ID 000473116801016

• Clinical Follow-Up after Imaging and Dosimetry for Yttrium-90 (Y-90) Liver Radioembolization Using a SiPM-Based PET/CT Scanner Duan, H., Khalaf, M., Baratto, L., Srinivas, S., Sze, D., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2019

  View details for Web of Science ID 000473116800126

• Comparison of three interpretation criteria of Ga-68-PS A PET based on in er and intra-reader agreement Toriihara, A., Nobashi, T., Baratto, L., Park, S., Hatami, N., Duan, H., Aparici, C., Davidzon, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2019

  View details for Web of Science ID 000473116801600

• Preliminary Results of a Prospective Study of Ga-68-RM2 PET/MRI for Detection of Recurrent Prostate Cancer in Patients with Negative Conventional Imaging Baratto, L., Duan, H., Harrison, C., Hatami, N., Aparici, C., Davidzon, G., Yohannan, T., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2019

  View details for Web of Science ID 000473116801014

• Prospective evaluation of F-18- DCFPyL in Patients with Biochemically Recurrent Prostate Cancer: Positivity Rate and Correlation with PSA levels Harrison, C., Song, H., Franc, B. L., Guja, K., Moradi, F., Davidzon, G., Aparici, C., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2019

  View details for Web of Science ID 000473116801610

• Prospective Comparison of F-18-DCFPyL PET/CT with F-18-NaF PET/CT for Detection of Skeletal Metastases in Biochemically Recurrent Prostate Cancer Duan, H., Song, H., Baratto, L., Khalaf, M., Hatami, N., Franc, B., Moradi, F., Davidzon, G., Aparici, C., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2019

  View details for Web of Science ID 000473116801621

• Prospective evaluation of Ga-68-RM2 PET/MRI and Ga-68-PSMA11 PET/CT in patients with biochemical recurrence of prostate cancer Baratto, L., Duan, H., Hatami, N., Toriihara, A., Song, H., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2019

  View details for Web of Science ID 000473116800587

• Quantification of uptake in Ga-68-DOTATATE PET: Correlation between standardized uptake values and patient factors Moradi, F., Guja, K., Aparici, C., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2019

  View details for Web of Science ID 000473116800434

• Serial Cardiac FDG-PET for the Diagnosis and Therapeutic Guidance of Patients With Cardiac Sarcoidosis JOURNAL OF CARDIAC FAILURE Ning, N., Guo, H., Iagaru, A., Mittra, E., Fowler, M., Witteles, R. 2019; 25 (4): 307–11

  View details for DOI 10.1016/j.cardfail.2019.02.018

  View details for Web of Science ID 000466060500013

• 18F-FPPRGD2 PET/CT in patients with metastatic renal cell cancer. European journal of nuclear medicine and molecular imaging Toriihara, A., Duan, H., Thompson, H. M., Park, S., Hatami, N., Baratto, L., Fan, A. C., Iagaru, A. 2019

  Abstract

  PURPOSE: The usefulness of positron emission tomography/computed tomography (PET/CT) using (18F)-2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid peptide [PEG3-E{c(RGDyk)}2] (18F-FPPRGD2) in patients with metastatic renal cell cancer (mRCC) has not been evaluated; therefore, we were prompted to conduct this pilot study.METHODS: Seven patients with mRCC were enrolled in this prospective study. 18F-FPPRGD2 and 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) PET/CT images were evaluated in a per-lesion analysis. Maximum standardized uptake value (SUVmax) and tumor-to-background ratio (T/B) were measured for all detected lesions, both before and after starting antiangiogenic therapy.RESULTS: Sixty lesions in total were detected in this cohort. SUVmax from 18F-FPPRGD2 PET/CT was lower than that from 18F-FDG PET/CT (4.4±2.9 vs 7.8±5.6, P<0.001). Both SUVmax and T/B from 18F-FPPRGD2 PET/CT decreased after starting antiangiogenic therapy (SUVmax, 4.2±3.2 vs 2.6±1.4, P=0.003; T/B, 3.7±3.2 vs 1.5±0.8, P<0.001). Average changes in SUVmax and T/B were-29.3±23.6% and-48.1±28.3%, respectively.CONCLUSIONS: 18F-FPPRGD2 PET/CT may be an useful tool for monitoring early response to antiangiogenic therapy in patients with mRCC. These preliminary results need to be confirmed in larger cohorts.

  View details for PubMedID 30850872

• Serial Cardiac FDG-PET for the Diagnosis and Therapeutic Guidance of Patients with Cardiac Sarcoidosis. Journal of cardiac failure Ning, N., Guo, H. H., Iagaru, A., Mittra, E., Fowler, M., Witteles, R. 2019

  Abstract

  BACKGROUND: Cardiac fluorodeoxyglucose positron emission tomography (FDG-PET) has emerged as a standard imaging modality for the diagnosis of cardiac sarcoidosis (CS); however, there is a scarcity of data on the use of serial FDG-PET to guide immunosuppressive therapy.OBJECTIVES: To report our experience in using serial FDG-PET for the diagnosis and management of patients with CS, focusing on its utility in ongoing immunosuppression management.METHODS: We studied consecutive patients with CS managed at Stanford University from 2010-2017. We evaluated our experience in using FDG-PET for diagnosis and guidance of immunosuppressive therapy titration in CS.RESULTS: Among 34 patients diagnosed with CS, 16 (47%), 12 (35%) and 14 (41%) patients presented with heart block, heart failure and ventricular arrhythmias, respectively. FDG-PET proved beneficial in the initial diagnosis in 21 (62%) patients. 128 FDG-PET scans were performed (median 3/patient). Ninety-four (73%) FDG-PET scans resulted in a change in therapy, with 42 (33%) FDG-PET scans instrumental for tapering prednisone. Among patients who were initiated on prednisone, the mean dose of prednisone at one year was 9.5 mg/day. Over a median follow-up of 2.3 years, 48% of patients were successfully weaned off of prednisone completely, and 20% were weaned to a maintenance dosage of 5-10 mg/day. During the follow-up period, transplant-free survival was 88%.CONCLUSIONS: The use of serial cardiac FDG-PET for the diagnosis and management of CS was critical for guiding immunosuppression management and resulted in low chronic steroid doses and good disease control within one year of diagnosis.

  View details for PubMedID 30825644

• Multimodality Hyperpolarized C-13 MRS/PET/Multiparametric MR Imaging for Detection and Image-Guided Biopsy of Prostate Cancer: First Experience in a Canine Prostate Cancer Model. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Bachawal, S. V., Park, J. M., Valluru, K. S., Loft, M. D., Felt, S. A., Vilches-Moure, J. G., Saenz, Y. F., Daniel, B., Iagaru, A., Sonn, G., Cheng, Z., Spielman, D. M., Willmann, J. K. 2019

  Abstract

  PURPOSE: To assess whether simultaneous hyperpolarized C-13 magnetic resonance spectroscopy (MRS)/positron emission tomography (PET)/multiparametric magnetic resonance (mpMR) imaging is feasible in an orthotopic canine prostate cancer (PCa) model using a clinical PET/MR system and whether the combined imaging datasets can be fused with transrectal ultrasound (TRUS) in real time for multimodal image fusion-guided targeted biopsy of PCa.PROCEDURES: Institutional Animal Care and Use Committee approval was obtained for this study. Canine prostate adenocarcinoma (Ace-1) cells were orthotopically injected into the prostate of four dogs. Once tumor engraftment was confirmed by TRUS, simultaneous hyperpolarized C-13 MRS of [1-13C]pyruvate, PET (2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), [68Ga]NODAGA-SCH1), and mpMR (T2W, DWI) imaging was performed using a clinical PET/MR system. Multimodality imaging data sets were then fused with TRUS and image-guided targeted biopsy was performed. Imaging results were then correlated with histological findings.RESULTS: Successful tumor engraftment was histologically confirmed in three of the four dogs (dogs 2, 3, and 4) and simultaneous C-13 MRS/PET/mpMR was feasible in all three. In dog 2, C-13 MRS showed increased lactate signal in the tumor (lactate/totalC=0.47) whereas mpMR did not show any signal changes. In dog 3, [18F]FDG-PET (SUVmean=1.90) and C-13 MRS (lactate/totalC=0.59) showed elevated metabolic activity in the tumor. In dog 4, [18F]FDG (SUVmean=2.43), [68Ga]NODAGA-SCH1 (SUVmean=0.75), and C-13 MRS (Lac/totalC=0.53) showed elevated uptake in tumor compared to control tissue and multimodal image fusion-guided biopsy of the tumor was successfully performed.CONCLUSION: Simultaneous C-13 MRS/PET/mpMR imaging and multimodal image fusion-guided biopsy is feasible in a canine PCa model.

  View details for PubMedID 30793241

• Imaging gastrin-releasing peptide receptors (GRPRs) in prostate cancer CLINICAL AND TRANSLATIONAL IMAGING Baratto, L., Laudicella, R., Picchio, M., Baldari, S., Iagaru, A. 2019; 7 (1): 39–44

  View details for DOI 10.1007/s40336-018-00308-x

  View details for Web of Science ID 000458743500006

• Improved Scatter Correction to Eliminate Halo-Artifacts for 68Ga-labeled Radiopharmaceuticals in PET Imaging. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Wangerin, K. A., Iagaru, A. n. 2019

  View details for PubMedID 31076503

• Optimization of 89Zr PET imaging for improved multi-site quantification and lesion detection using an anthropomorphic phantom. Journal of nuclear medicine technology Christian, P. E., Williams, S. P., Burrell, L. D., Castaneda, P. n., Albani, J. n., Sandella, N. n., Iagaru, A. n., Hoffman, J. M., de Crespigny, A. n., Sanabria Bohorquez, S. M. 2019

  Abstract

  Objective: To harmonize multicenter 89Zr PET imaging for oncology trials and to evaluate lesion detection. Methods: Seven PET scanners were evaluated using a custom chest oncology phantom with nine spherical lesions, 7-20 mm in diameter. A 4:1 lesion to background ratio simulating a patient dose of 92.5 MBq. Various image reconstructions were evaluated. Images were assessed for lesion detection and recovery coefficients (RC) and background signal variance were measured. Results: Two scanners failed to meet the quality control criteria. Optimal reconstruction algorithms enabling adequate lesion detection and reliable quantification across the other five scanners were determined without compromising the data quality. On average, 95% of the 10 mm lesions were detected and the 7 mm lesion was visualized in only one scanner. The background variance range was 8.6 to 16%. Conclusion: We established multicenter harmonization procedures for 89Zr PET imaging in oncology, optimizing small lesion (≥10 mm) detectability and accurate quantification.

  View details for DOI 10.2967/jnmt.119.230474

  View details for PubMedID 31604892

• The Role of PET/CT in the Imaging of Pancreatic Neoplasms. Seminars in ultrasound, CT, and MR Duan, H. n., Baratto, L. n., Iagaru, A. n. 2019; 40 (6): 500–508

  Abstract

  Pancreas cancer is a complex disease and its prognosis is related to the origin of the tumor cell as well as the stage of disease at the time of diagnosis. Pancreatic adenocarcinomas derive from the exocrine pancreas and are the fourth leading cause of cancer-related deaths in the United States, while well-differentiated pancreatic neuroendocrine tumors (pNETs) derived from the endocrine part of the pancreas are rare and characterized by a slow growth and good life expectancy. Surgery is the only curative treatment approach, and an accurate assessment of resectability is of paramount importance in order to avoid futile procedures. The role of molecular imaging with positron emission tomography and computed tomography ranges from indispensable for pNETs to controversial for certain scenarios in pancreatic adenocarcinomas. This review article aims to overview molecular pancreatic imaging.

  View details for DOI 10.1053/j.sult.2019.04.006

  View details for PubMedID 31806148

• Initial experience with a PET/computed tomography system using silicon photomultiplier detectors. Nuclear medicine communications Park, S. Y., Barrato, L. n., Hatami, N. n., Davidzon, G. n., Gambhir, S. S., Iagaru, A. n. 2019

  Abstract

  A PET/computed tomography (CT) that uses silicon photomultiplier (SiPM) technology was installed at our institution. Here, we report the initial use of the new scanner and evaluate the image quality in comparison to standard PET/CT scanners.Seventy-two patients were scanned first using standard PET/CT followed immediately by the new PET/CT system. Images from the new PET/CT system were reconstructed using a conventional [non time-of-flight (TOF)] algorithm, TOF alone and TOF in combination with BSREM. Images from standard PET/CT were reconstructed using clinical standard-of-care settings. Three blinded readers randomly reviewed four datasets (standard, non-TOF, TOF alone, TOF+BSREM) per patient for image quality using a five-point Likert scale. SUV measurements for the single most avid lesion on each dataset were also recorded.Datasets from the new scanner had higher image quality (P < 0.001) and SUV measurements (P < 0.001) compared with the standard scanners, and scores further improved when TOF and BSREM algorithms were added (mean scores for standard, non-TOF, TOF alone and TOF+BSREM were 3.1, 3.9, 4.3 and 5.0, respectively; mean SUVmax for hottest lesion were 8.8, 10.3, 10.7 and 13.3, respectively).The SiPM-based PET/CT system outperforms two standard Bismuth germanium oxide- and Lutetium-yttrium oxyorthosilicate-based scanners in terms of image quality, with further benefits added using TOF and BSREM. This may be beneficial for detecting small lesions and more accurate disease staging.

  View details for DOI 10.1097/MNM.0000000000001088

  View details for PubMedID 31568189

• Performance Comparison of Individual and Ensemble CNN Models for the Classification of Brain 18F-FDG-PET Scans. Journal of digital imaging Nobashi, T. n., Zacharias, C. n., Ellis, J. K., Ferri, V. n., Koran, M. E., Franc, B. L., Iagaru, A. n., Davidzon, G. A. 2019

  Abstract

  The high-background glucose metabolism of normal gray matter on [18F]-fluoro-2-D-deoxyglucose (FDG) positron emission tomography (PET) of the brain results in a low signal-to-background ratio, potentially increasing the possibility of missing important findings in patients with intracranial malignancies. To explore the strategy of using a deep learning classifier to aid in distinguishing normal versus abnormal findings on PET brain images, this study evaluated the performance of a two-dimensional convolutional neural network (2D-CNN) to classify FDG PET brain scans as normal (N) or abnormal (A).Two hundred eighty-nine brain FDG-PET scans (N; n = 150, A; n = 139) resulting in a total of 68,260 images were included. Nine individual 2D-CNN models with three different window settings for axial, coronal, and sagittal axes were trained and validated. The performance of these individual and ensemble models was evaluated and compared using a test dataset. Odds ratio, Akaike's information criterion (AIC), and area under curve (AUC) on receiver-operative-characteristic curve, accuracy, and standard deviation (SD) were calculated.An optimal window setting to classify normal and abnormal scans was different for each axis of the individual models. An ensembled model using different axes with an optimized window setting (window-triad) showed better performance than ensembled models using the same axis and different windows settings (axis-triad). Increase in odds ratio and decrease in SD were observed in both axis-triad and window-triad models compared with individual models, whereas improvements of AUC and AIC were seen in window-triad models. An overall model averaging the probabilities of all individual models showed the best accuracy of 82.0%.Data ensemble using different window settings and axes was effective to improve 2D-CNN performance parameters for the classification of brain FDG-PET scans. If prospectively validated with a larger cohort of patients, similar models could provide decision support in a clinical setting.

  View details for DOI 10.1007/s10278-019-00289-x

  View details for PubMedID 31659587

• Comparison of three interpretation criteria of 68Ga-PSMA11 PET based on inter- and intra-reader agreement. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Toriihara, A. n., Nobashi, T. n., Baratto, L. n., Duan, H. n., Moradi, F. n., Park, S. n., Hatami, N. n., Aparici, C. n., Davidzon, G. n., Iagaru, A. n. 2019

  Abstract

  Positron emission tomography (PET) using radiolabeled prostate specific membrane antigen (PSMA) is now more and more widely adopted as a valuable tool to evaluate patients with prostate cancer (PC). Recently, three different criteria for interpretation of PSMA PET were published: European Association of Nuclear Medicine (EANM) criteria, prostate cancer molecular imaging standardized evaluation (PROMISE) criteria, and PSMA-reporting and data system (PSMA-RADS). We compared these three criteria in terms of inter-reader, intra-reader, and inter-criteria agreement. Methods: Data from 104 patients prospectively enrolled in research protocols at our institution were retrospectively reviewed. The cohort consisted of two groups: 47 patients (mean age: 64.2 years old) who underwent Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)] (68Ga-PSMA11) PET/magnetic resonance imaging (MRI) for initial staging of biopsy-proven intermediate- or high-risk PC, and 57 patients (mean age: 70.5 years old) who underwent 68Ga-PSMA11 PET/computed tomography (CT) due to biochemically recurrent (BCR) PC. Three nuclear medicine physicians independently evaluated all 68Ga-PSMA11 PET/MRI and PET/CT studies according to the three interpretation criteria. Two of them reevaluated all studies 6 months later in the same manner and blinded to the initial reading. Gwet's AC was calculated to evaluate inter- and intra-reader, and inter-criteria agreement based on the following sites: local lesion (primary tumor or prostate bed after radical prostatectomy), lymph node metastases, and other metastases. Results: In the PET/MRI group, inter-reader, intra-reader, and inter-criteria agreements were substantial to almost perfect in any sites according to all of the three criteria. In the PET/CT group, inter-reader agreement was substantial to almost perfect except judgement of distant metastases based on PSMA-RADS (Gwet's AC = 0.57, moderate agreement), in which the most frequent cause of disagreement was lung nodules. Intra-reader agreements were substantial to almost perfect in any sites according to all of the three criteria. Inter-criteria agreements of each site were also substantial to almost perfect. Conclusion: Although the three published criteria have good inter-reader and intra-reader reproducibility in evaluating 68Ga-PSMA11 PET, there are factors bringing inter-reader disagreement. This indicates that further work is needed to address the issue.

  View details for DOI 10.2967/jnumed.119.232504

  View details for PubMedID 31562226

• 68Ga Scatter Correction to Eliminate Halo-Artifacts in PET Imaging. Urology Wangerin, K. n., Iagaru, A. n. 2019

  View details for DOI 10.1016/j.urology.2019.05.037

  View details for PubMedID 31195009

• Prognostic value of somatostatin receptor expressing tumor volume calculated from 68Ga-DOTATATE PET/CT in patients with well-differentiated neuroendocrine tumors. European journal of nuclear medicine and molecular imaging Toriihara, A. n., Baratto, L. n., Nobashi, T. n., Park, S. n., Hatami, N. n., Davidzon, G. n., Kunz, P. L., Iagaru, A. n. 2019

  Abstract

  To evaluate the prognostic value of volumetric parameters calculated from 68Ga-1,4,7,10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Thr3-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT) in patients with well-differentiated neuroendocrine tumor (WD-NET).Ninety-two patients (44 men and 48 women, mean age of 59.5-year-old) with pathologically confirmed WD-NET (grades 1 or 2) were enrolled in a prospective expanded access protocol. Selected data was analyzed retrospectively for this project. Maximum standardized uptake value (SUVmax) in the lesion with the highest 68Ga-DOTATATE uptake was measured and recorded for each patient. In addition, two volumetric parameters, namely, somatostatin receptor expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE), were calculated in each 68Ga-DOTATATE-avid lesion. SRETV was defined as tumor volume with higher 68Ga-DOTATATE uptake than the 50% of SUVmax within the volume of interest (VOI) for each lesion. TLSRE was calculated by multiplying SRETV and mean SUV within the same VOI. Thereafter, the sum of SRETV (ΣSRETV) and TLSRE (ΣTLSRE) for all detected lesions per patient were calculated. Progression-free survival (PFS) was set as primary endpoint. Kaplan-Meier survival analysis, log-rank test, and Cox's proportional hazard model were used for statistical analysis.Univariate analyses revealed significant difference of PFS for WHO tumor grade and ΣSRETV (P < 0.05), while there were no significant differences in age, sex, SUVmax, and ΣTLSRE (P > 0.05). Multivariate analysis identified WHO tumor grade and ΣSRETV as independent predictors of PFS.ΣSRETV calculated from 68Ga-DOTATATE PET/CT may have prognostic value of PFS in WD-NET patients.

  View details for DOI 10.1007/s00259-019-04455-9

  View details for PubMedID 31350603

• NCCN Guidelines Insights: Thyroid Carcinoma, Version 2.2018. Journal of the National Comprehensive Cancer Network : JNCCN Haddad, R. I., Nasr, C., Bischoff, L., Busaidy, N. L., Byrd, D., Callender, G., Dickson, P., Duh, Q., Ehya, H., Goldner, W., Haymart, M., Hoh, C., Hunt, J. P., Iagaru, A., Kandeel, F., Kopp, P., Lamonica, D. M., McIver, B., Raeburn, C. D., Ridge, J. A., Ringel, M. D., Scheri, R. P., Shah, J. P., Sippel, R., Smallridge, R. C., Sturgeon, C., Wang, T. N., Wirth, L. J., Wong, R. J., Johnson-Chilla, A., Hoffmann, K. G., Gurski, L. A. 2018; 16 (12): 1429–40

  Abstract

  The NCCN Guidelines for Thyroid Carcinoma provide recommendations for the management of different types of thyroid carcinoma, including papillary, follicular, Hurthle cell, medullary, and anaplastic carcinomas. These NCCN Guidelines Insights summarize the panel discussion behind recent updates to the guidelines, including the expanding role of molecular testing for differentiated thyroid carcinoma, implications of the new pathologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and the addition of a new targeted therapy option for BRAF V600E-mutated anaplastic thyroid carcinoma.

  View details for PubMedID 30545990

• Ga-68-RM2 PET/MRI Detection of Recurrent Prostate Cancer in Patients with Negative Conventional Imaging Baratto, L., Duan, H., Harrison, C., Mari, C., Davidzon, G., Yohannan, T., Iagaru, A. SPRINGER. 2018: S151–S152

  View details for Web of Science ID 000449266201100

• Diagnostic 123I Whole Body Scan Prior to Ablation of Thyroid Remnant in Patients With Papillary Thyroid Cancer: Implications for Clinical Management CLINICAL NUCLEAR MEDICINE Song, H., Mosci, C., Akatsu, H., Basina, M., Dosiou, C., Iagaru, A. 2018; 43 (10): 705–9

  Abstract

  The use of I whole body scintigraphy (WBS) before I radioiodine ablation (RIA) of the post-surgical thyroid remnant in patients with papillary thyroid cancer (PTC) remains debated. The American Thyroid Association's guidelines state that WBS may be useful before RIA (rating C-expert opinion). Some institutions do not use I WBS before RIA in their routine clinical protocol. We were therefore prompted to evaluate the impact of I WBS prior to ablation of thyroid remnant in patients with PTC.We reviewed data from 152 consecutive patients with PTC who had total thyroidectomy and were referred for RIA between August 2007 and February 2009 at our institution. The group included 107 women and 45 men, 13-82 years old (mean ± SD: 45.5 ± 18.3). Three endocrinologists blinded to the results of the I WBS reviewed patients' data including sex, age, pathology, thyroglobulin (Tg) level, anti-Tg antibodies, thyroid stimulating hormone (TSH) level and ultrasound results. Each endocrinologist then returned a form with the recommended I dose for each participant, according to the following rules: 50-75 mCi (remnant ablation), 75-125 mCi (lymph nodes metastases), 150 mCi (lung metastases), and 200 mCi (bone metastases). We compared their recommended doses with the actual I doses prescribed after the pre-therapy I WBS.All three endocrinologists recommended the same dose in 98.7% of the cases. The dose prescribed by the endocrinologists matched the dose administered after analyzing the I WBS in 77 patients (51%). However, for 46 patients (30%) the endocrinologists would have given a lower dose, for 18 patients (12%) a higher dose than that administered based on the results of the I WBS, while 11 patients (7%) would have been treated unnecessarily (5/11 had no I uptake and 6/11 had I uptake in the breasts).Our study suggests a significant role of the pre-therapy I WBS in PTC patients referred for I ablation post-thyroidectomy. The actual I dose that was administered based on the I WBS differed from the dose recommended in the absence of the I WBS in 49% of the cases.

  View details for PubMedID 30153149

• Ga-68-RM2 PET vs. Ga-68-PSMA-11 PET: Prospective Comparison in Patients with Biochemical Recurrence of Prostate Cancer Baratto, L., Duan, H., Minamimoto, R., Mari, C., Yohannan, T., Davidzon, G., Iagaru, A. SPRINGER. 2018: S151

  View details for Web of Science ID 000449266201099

• Ga-68-PSMA-11 Imaging for Biochemical Relapse of Prostate Cancer Using Dual-Time LYSO and SiPM-Based Detectors PET/CT Duan, H., Park, S., Baratto, L., Hatami, N., Khalaf, M. H., Yohannan, T. K., Davidzon, G. A., Iagaru, A. H. SPRINGER. 2018: S713

  View details for Web of Science ID 000449266206215

• High Quality Imaging and Dosimetry of Yttrium-90 (Y-90) SIRT Using a Digital PET/CT Duan, H., Khalaf, M. H., Baratto, L., Sze, D., Srinivas, S. M., Iagaru, A. H. SPRINGER. 2018: S197

  View details for Web of Science ID 000449266201193

• Dual-Time Ga-68-RM2 Imaging for Staging Patients with Newly Diagnosed Intermediate or High Risk Prostate Cancer Using PMT and SiPM-Based Detectors PET/CT Baratto, L., Duan, H., Hatami, N., Yohannan, T., Mari, C., Davidzon, G., Iagaru, A. SPRINGER. 2018: S724

  View details for Web of Science ID 000449266206241

• Standardized uptake value atlas: physiological and abnormal Ga-68-RM2 uptake in patients with prostate cancer Baratto, L., Duan, H., Torihara, A., Hatami, N., Laudicella, R., Nobashi, T., Iagaru, A. SPRINGER. 2018: S526–S527

  View details for Web of Science ID 000449266205022

• Clinical Evaluation of Ga-68-PSMA-Iota Iota and Ga-68-RM2 PET Images Reconstructed With an Improved Scatter Correction Algorithm AMERICAN JOURNAL OF ROENTGENOLOGY Wangerin, K. A., Baratto, L., Khalighi, M., Hope, T. A., Gulaka, P. K., Deller, T. W., Iagaru, A. H. 2018; 211 (3): 655–60

  Abstract

  Gallium-68-labeled radiopharmaceuticals pose a challenge for scatter estimation because their targeted nature can produce high contrast in these regions of the kidneys and bladder. Even small errors in the scatter estimate can result in washout artifacts. Administration of diuretics can reduce these artifacts, but they may result in adverse events. Here, we investigated the ability of algorithmic modifications to mitigate washout artifacts and eliminate the need for diuretics or other interventions.The model-based scatter algorithm was modified to account for PET/MRI scanner geometry and challenges of non-FDG tracers. Fifty-three clinical 68Ga-RM2 and 68Ga-PSMA-11 whole-body images were reconstructed using the baseline scatter algorithm. For comparison, reconstruction was also processed with modified sampling in the single-scatter estimation and with an offset in the scatter tail-scaling process. None of the patients received furosemide to attempt to decrease the accumulation of radiopharmaceuticals in the bladder. The images were scored independently by three blinded reviewers using the 5-point Likert scale.The scatter algorithm improvements significantly decreased or completely eliminated the washout artifacts. When comparing the baseline and most improved algorithm, the image quality increased and image artifacts were reduced for both 68Ga-RM2 and for 68Ga-PSMA-11 in the kidneys and bladder regions.Image reconstruction with the improved scatter correction algorithm mitigated washout artifacts and recovered diagnostic image quality in 68Ga PET, indicating that the use of diuretics may be avoided.

  View details for PubMedID 29873506

• Prostate Cancer Theranostics Targeting Gastrin-Releasing Peptide Receptors. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Baratto, L., Jadvar, H., Iagaru, A. 2018; 20 (4): 501–9

  Abstract

  Gastrin-releasing peptide receptors (GRPRs), part of the bombesin (BBN) family, are aberrantly overexpressed in many cancers, including those of the breast, prostate, pancreas, and lung, and therefore present an attractive target for cancer diagnosis and therapy. Different bombesin analogs have been radiolabeled and used for imaging diagnosis, staging, evaluation of biochemical recurrence, and assessment of metastatic disease in patients with prostate cancer. Recently, interest has shifted from BBN-like receptor agonists to antagonists, because the latter does not induce adverse effects and demonstrate superior in vivo pharmacokinetics. We review the preclinical and clinical literatures on the use of GRPRs as targets for imaging and therapy of prostate cancer, with a focus on the newer developments and theranostic potential of GRPR peptides.

  View details for PubMedID 29256046

• Combined 68Ga-NOTA-PRGD2 and 18F-FDG PET/CT Can Discriminate Uncommon Meningioma Mimicking High-Grade Glioma. Clinical nuclear medicine Li, D., Zhang, J., Ji, N., Zhao, X., Zheng, K., Qiao, Z., Li, F., Lang, L., Iagaru, A., Niu, G., Zhu, Z., Chen, X. 2018

  Abstract

  OBJECTIVES: Uncommon pathological subtypes of meningioma may present with severe peritumoral brain edema and mimic high-grade glioma (HGG). In a prospective cohort study of Ga-NOTA-PRGD2 PET/CT to evaluate glioma, we occasionally observed that a combination of Ga-NOTA-PRGD2 and F-FDG was able to differentiate these 2 lesion types.METHODS: From 2013 to 2016, 21 patients suspected of HGG by MRI were recruited for evaluation using Ga-NOTA-PRGD2 PET/CT. Brain F-FDG PET/CT was performed within 3 days for comparison, and the tumor was surgically removed. The PET results were compared with integrin alphavbeta3 expression and microvascular density quantification of tumor samples.RESULTS: Of the 21 recruited patients, 5 patients were finally pathologically diagnosed as uncommon meningioma with severe peritumoral brain edema, including chordoid meningioma (n = 1), angiomatous meningioma (n = 1), and mixed angiomatous and microcystic meningioma (n = 3). Sixteen were diagnosed as HGG. All the meningioma lesions (n = 5) exhibited intense and homogeneous Ga-NOTA-PRGD2 uptake with higher SUVmax on Ga-NOTA-PRGD2 PET (1.64-7.86; mean ± SD, 4.23 ± 2.48) than the HGG lesions (0.81-2.99; mean ± SD, 1.57 ± 0.33; P = 0.0047). Moreover, the uptake ratios of Ga-NOTA-PRGD2 over F-FDG, normalized as lg100 * SUVmax (RGD / FDG), in the uncommon meningiomas were significantly higher than those in HGG (1.87 ± 1.36 vs 1.04 ± 0.87, P = 0.0001). A cutoff value of 1.58 was able to discriminate between these lesion types. There were positive correlations among the expression level of integrin alphavbeta3, microvascular density, and the tumor-to-background ratio derived from Ga-NOTA-PRGD2 PET (P < 0.05).CONCLUSIONS: This study reveals a specific imaging pattern of uncommon meningioma mimicking HGG, in which Ga-NOTA-PRGD2 PET provided added value to F-FDG PET.

  View details for PubMedID 30052597

• 18F-florbetaben whole-body PET/MRI for evaluation of systemic amyloid deposition. EJNMMI research Baratto, L., Park, S. Y., Hatami, N., Gulaka, P., Vasanawala, S., Yohannan, T. K., Herfkens, R., Witteles, R., Iagaru, A. 2018; 8 (1): 66

  Abstract

  BACKGROUND: Florbetaben, a 18F-labeled stilbene derivative (Neuraceq, formerly known as BAY-949172), is a diagnostic radiopharmaceutical developed to visualize beta-amyloid plaques in the brain. Here, we report a pilot study evaluating patients with suspected cardiac amyloidosis for systemic extent of disease.METHODS: We prospectively enrolled nine patients, 61-86year old (mean±SD 69.4±8.6), referred from the cardiac amyloid clinic. First, dynamic imaging of the heart was acquired immediately after injection of 222-318.2MBq (mean±SD 270.1±33.3) of 18F-florbetaben using the GE SIGNA PET/MRI. This was followed by a whole-body PET/MRI scan 60-146.4min (mean±SD 98±33.4) after injection. Cardiac MRI sequences included ECG-triggered cine SSFP, T2-weighted, and late gadolinium-enhanced imaging. Whole-body MRI sequences included MRAC and axial T1-weighted imaging.RESULTS: High early uptake and delayed high uptake in the left ventricle correlated with amyloid deposition in five patients, while low uptake on early and delayed cardiac imaging was noted in four patients. Cardiac function measurements were successfully obtained in all participants. Areas of increased abnormal 18F-florbetaben accumulation were noted on delayed whole-body imaging in the bone marrow (seven patients), stomach (diffuse in five patients and focal in one patient), brain (five patients), salivary glands (three patients), tongue (three patients), spleen (three patients), skeletal muscles (three patients), ocular muscles (two patients), thyroid (two patients), pleura (two patients), kidneys (two patients), and lungs (two patients).CONCLUSIONS: Whole-body 18F-florbetaben PET/MRI is promising for localization of systemic amyloid deposition. This technique may provide important structural and functional information regarding the organs involved by disease, with potential to guide biopsy and evaluate response to treatment.TRIAL REGISTRATION: Clinicaltrials.gov registration: NCT03119558 .

  View details for PubMedID 30043115

• Nuclear Medicine Imaging Techniques for Detection of Skeletal Metastases in Breast Cancer PET CLINICS Iagaru, A., Minamimoto, R. 2018; 13 (3): 383-+

  View details for DOI 10.1016/j.cpet.2018.02.002

  View details for Web of Science ID 000437191800007

• Nuclear Medicine Imaging Techniques for Detection of Skeletal Metastases in Breast Cancer. PET clinics Iagaru, A., Minamimoto, R. 2018; 13 (3): 383-393

  Abstract

  Bone is the most common site of metastases from advanced breast cancer. Whole-body bone scintigraphy has been most frequently used in the process of managing cancer patients; its advantage is that it provides rapid whole-body imaging for screening of osteoblastic or sclerotic/mixed bone metastases at reasonable cost. Recent advanced techniques, such as single-photon emission computed tomography (SPECT)/CT, quantitative analysis, and bone scan index, contribute to better understanding of the disease state. More recent advances in machines and PET drugs improve the staging of the skeleton with higher sensitivity and specificity.

  View details for DOI 10.1016/j.cpet.2018.02.002

  View details for PubMedID 30100077

• Gallium 68 PSMA-11 PET/MR Imaging in Patients with Intermediate- or High-Risk Prostate Cancer. Radiology Park, S. Y., Zacharias, C., Harrison, C., Fan, R. E., Kunder, C., Hatami, N., Giesel, F., Ghanouni, P., Daniel, B., Loening, A. M., Sonn, G. A., Iagaru, A. 2018: 172232

  Abstract

  Purpose To report the results of dual-time-point gallium 68 (68Ga) prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/magnetic resonance (MR) imaging prior to prostatectomy in patients with intermediate- or high-risk cancer. Materials and Methods Thirty-three men who underwent conventional imaging as clinically indicated and who were scheduled for radical prostatectomy with pelvic lymph node dissection were recruited for this study. A mean dose of 4.1 mCi ± 0.7 (151.7 MBq ± 25.9) of 68Ga-PSMA-11 was administered. Whole-body images were acquired starting 41-61 minutes after injection by using a GE SIGNA PET/MR imaging unit, followed by an additional pelvic PET/MR imaging acquisition at 87-125 minutes after injection. PET/MR imaging findings were compared with findings at multiparametric MR imaging (including diffusion-weighted imaging, T2-weighted imaging, and dynamic contrast material-enhanced imaging) and were correlated with results of final whole-mount pathologic examination and pelvic nodal dissection to yield sensitivity and specificity. Dual-time-point metabolic parameters (eg, maximum standardized uptake value [SUVmax]) were compared by using a paired t test and were correlated with clinical and histopathologic variables including prostate-specific antigen level, Gleason score, and tumor volume. Results Prostate cancer was seen at 68Ga-PSMA-11 PET in all 33 patients, whereas multiparametric MR imaging depicted Prostate Imaging Reporting and Data System (PI-RADS) 4 or 5 lesions in 26 patients and PI-RADS 3 lesions in four patients. Focal uptake was seen in the pelvic lymph nodes in five patients. Pathologic examination confirmed prostate cancer in all patients, as well as nodal metastasis in three. All patients with normal pelvic nodes in PET/MR imaging had no metastases at pathologic examination. The accumulation of 68Ga-PSMA-11 increased at later acquisition times, with higher mean SUVmax (15.3 vs 12.3, P < .001). One additional prostate cancer was identified only at delayed imaging. Conclusion This study found that 68Ga-PSMA-11 PET can be used to identify prostate cancer, while MR imaging provides detailed anatomic guidance. Hence, 68Ga-PSMA-11 PET/MR imaging provides valuable diagnostic information and may inform the need for and extent of pelvic node dissection.

  View details for PubMedID 29786490

• Initial experience with a SiPM-based PET/CT scanner: influence of acquisition time on image quality EJNMMI PHYSICS Sonni, I., Baratto, L., Park, S., Hatami, N., Srinivas, S., Davidzon, G., Gambhir, S., Iagaru, A. 2018; 5: 9

  Abstract

  A newly introduced PET/CT scanner (Discovery Meaningful Insights-DMI, GE Healthcare) includes the silicon photomultiplier (SiPM) with time-of-flight (TOF) technology first used in the GE SIGNA PET/MRI. In this study, we investigated the impact of various acquisition times on image quality using this SiPM-based PET/CT.We reviewed data from 58 participants with cancer who were scanned using the DMI PET/CT scanner. The administered dosages ranged 295.3-429.9 MBq (mean ± SD 356.3 ± 37.4) and imaging started at 71-142 min (mean ± SD 101.41 ± 17.52) after administration of the radiopharmaceutical. The patients' BMI ranged 19.79-46.16 (mean ± SD 26.55 ± 5.53). We retrospectively reconstructed the raw TOF data at 30, 60, 90, and 120 s/bed and at the standard image acquisition time per clinical protocol (180 or 210 s/bed depending on BMI). Each reconstruction was reviewed blindly by two nuclear medicine physicians and scored 1-5 (1-poor, 5-excellent quality). The liver signal-to-noise ratio (SNR) was used as a quantitative measure of image quality.The average scores ± SD of the readers were 2.61 ± 0.83, 3.70 ± 0.92, 4.36 ± 0.82, 4.82 ± 0.39, and 4.91 ± 0.91 for the 30, 60, 90, and 120 s/bed and at standard acquisition time, respectively. Inter-reader agreement on image quality assessment was good, with a weighted kappa of 0.80 (95% CI 0.72-0.81). In the evaluation of the effects of time per bed acquisition on semi-quantitative measurements, we found that the only time point significantly different from the standard time were 30 and 60 s (both with P < 0.001). The effects of dose and BMI were not statistically significant (P = 0.195 and 0.098, respectively). There was a significant positive effect of time on SNR (P < 0.001), as well as a significant negative effect of weight (P < 0.001).Our results suggest that despite significant delays from injection to imaging (due to comparison with standard PET/CT) compared to standard clinical operations and even in a population with average BMI > 25, images can be acquired as fast as 90 s/bed using the SiPM PET/CT and still result in very good image quality (average score > 4).

  View details for PubMedID 29666972

• Intragastric Meal Distribution During Gastric Emptying Scintigraphy for Assessment of Fundic Accommodation: Correlation with Symptoms of Gastroparesis JOURNAL OF NUCLEAR MEDICINE Orthey, P., Yu, D., Van Natta, M. L., Ramsey, F. V., Diaz, J. R., Bennett, P. A., Iagaru, A. H., Fragomeni, R., McCallum, R. W., Sarosiek, I., Hasler, W. L., Farrugia, G., Grover, M., Koch, K. L., Nguyen, L., Snape, W. J., Abell, T. L., Pasricha, P. J., Tonascia, J., Hamilton, F., Parkman, H. P., Maurer, A. H., NIH Gastroparesis Consortium 2018; 59 (4): 691–97

  Abstract

  Impaired fundic accommodation (FA) limits fundic relaxation and the ability to act as a reservoir for food. Assessing intragastric meal distribution (IMD) during gastric emptying scintigraphy (GES) allows for a simple measure of FA. The 3 goals of this study were to evaluate trained readers' (nuclear medicine and radiology physicians) visual assessments of FA from solid-meal GES; develop software to quantify GES IMD; and correlate symptoms of gastroparesis with IMD and gastric emptying. Methods: After training to achieve a consensus interpretation of GES FA, 4 readers interpreted FA in 148 GES studies from normal volunteers and patients. Mixture distribution and κ-agreement analyses were used to assess reader consistency and agreement of scoring of FA. Semiautomated software was used to quantify IMD (ratio of gastric counts in the proximal stomach to those in the total stomach) at 0, 1, 2, 3, and 4 h after ingestion of a meal. Receiver-operating-characteristic analysis was performed to optimize the diagnosis of abnormal IMD at 0 min (IMD0) with impaired FA. IMD0, GES, water load testing, and symptoms were then compared in 177 patients with symptoms of gastroparesis. Results: Reader pairwise weighted κ-values for the visual assessment of FA averaged 0.43 (moderate agreement) for normal FA versus impaired FA. Readers achieved 84.0% consensus and 85.8% reproducibility in assessing impaired FA. IMD0 based on the division of the stomach into proximal and distal halves averaged 0.809 (SD, 0.083) for normal FA and 0.447 (SD, 0.132) (P < 0.01) for impaired FA. On the basis of receiver-operating-characteristic analysis, the optimal cutoff for IMD0 discrimination of normal FA from impaired FA was 0.568 (sensitivity, 86.7%; specificity, 91.7%). Of 177 patients with symptoms of gastroparesis, 129 (72.9%) had delayed gastric emptying; 25 (14.1%) had abnormal IMD0 Low IMD0 (impaired FA) was associated with increased early satiety (P = 0.02). Conclusion: FA can be assessed visually during routine GES with moderate agreement and high reader consistency. Visual and quantitative assessments of FA during GES can yield additional information on gastric motility to help explain patients' symptoms.

  View details for PubMedID 28970332

• Radium-223 Safety, Efficacy, and Concurrent Use with Abiraterone or Enzalutamide: First US Experience from an Expanded Access Program ONCOLOGIST Sartor, O., Vogelzang, N. J., Sweeney, C., Fernandez, D. C., Almeida, F., Iagaru, A., Brown, A., Smith, M. R., Agrawal, M., Dicker, A. P., Garcia, J. A., Lutzky, J., Wong, Y., Petrenciuc, O., Gratt, J., Shore, N. D., Morris, M. J., US Expanded Access Program Investi 2018; 23 (2): 193–202

  Abstract

  In the phase III ALSYMPCA trial, metastatic castration-resistant prostate cancer (mCRPC) patients had few prior life-prolonging therapies. Following ALSYMPCA, which demonstrated radium-223 survival benefit, and before radium-223 U.S. commercial availability, an expanded access program (EAP) providing early-access radium-223 allowed life-prolonging therapies in current use.This phase II, open-label, single-arm, multicenter U.S. EAP (NCT01516762) enrolled patients with symptomatic mCRPC, ≥2 bone metastases, and no lung, liver, or brain metastases. Patients received radium-223 55 kBq/kg intravenously every 4 weeks × 6. Primary outcomes were acute and long-term safety. Additional analyses were done by number of radium-223 injections, and prior or concomitant abiraterone or enzalutamide use.Of 252 patients, 184 received radium-223: 165/184 (90%) had Eastern Cooperative Oncology Group (ECOG) performance status 0-1; 183 (99%) had prior systemic anticancer therapy. Treatment-related adverse events occurred in 93/184 (51%) patients during treatment and 11 (6%) during follow-up. Median overall survival was 17 months, with 134/184 (73%) patients censored because of short follow-up due to radium-223 approval. In post hoc analyses, patients with ≥3 prior anticancer medications, baseline ECOG performance status ≥2, and lower baseline hemoglobin were less likely to receive 5-6 radium-223 injections and unlikely to benefit from radium-223. Radium-223 was well tolerated regardless of concurrent or prior abiraterone or enzalutamide.Radium-223 was well tolerated, with no new safety concerns; safety was maintained with abiraterone or enzalutamide. Patients with more advanced disease were less likely to benefit from radium-223. Clinicians should consider baseline characteristics and therapy sequence for greatest clinical value.In this phase II U.S. expanded access program, radium-223 was well tolerated, with a median overall survival of 17 months in metastatic castration-resistant prostate cancer patients. In post hoc analyses, radium-223 was safe regardless of concurrent abiraterone or enzalutamide, and median overall survival appeared longer when radium-223 was used earlier in patients with less prior treatment. Patients with more advanced disease were less likely to benefit from radium-223. Clinicians should consider baseline clinical characteristics and therapy sequence to provide the greatest clinical value to patients.

  View details for PubMedID 29183960

  View details for PubMedCentralID PMC5813754

• Quantitative imaging of bone-cartilage interactions in ACL-injured patients with PET-MRI. Osteoarthritis and cartilage Kogan, F. n., Fan, A. P., Monu, U. n., Iagaru, A. n., Hargreaves, B. A., Gold, G. E. 2018

  Abstract

  To investigate changes in bone metabolism by positron emission tomography (PET), as well as spatial relationships between bone metabolism and magnetic resonance imaging (MRI) quantitative markers of early cartilage degradation, in anterior cruciate ligament (ACL)-reconstructed knees.Both knees of 15 participants with unilateral reconstructed ACL tears and unaffected contralateral knees were scanned using a simultaneous 3.0T PET-MRI system following injection of 18F-sodium fluoride (18F-NaF). The maximum pixel standardized uptake value (SUVmax) in the subchondral bone and the average T2 relaxation time in cartilage were measured in each knee in eight knee compartments. We tested differences in SUVmax and cartilage T2 relaxation times between the ACL-injured knee and the contralateral control knee as well as spatial relationships between these bone and cartilage changes.Significantly increased subchondral bone 18F-NaF SUVmax and cartilage T2 times were observed in the ACL-reconstructed knees (median [inter-quartile-range (IQR)]: 5.0 [5.8], 36.8 [3.6] ms) compared to the contralateral knees (median [IQR]: 1.9 [1.4], 34.4 [3.8] ms). A spatial relationship between the two markers was also seen. Using the contralateral knee as a control, we observed a significant correlation of r = 0.59 between the difference in subchondral bone SUVmax (between injured and contralateral knees) and the adjacent cartilage T2 (between the two knees) [P < 0.001], with a slope of 0.49 ms/a.u. This correlation and slope were higher in deep layers (r = 0.73, slope = 0.60 ms/a.u.) of cartilage compared to superficial layers (r = 0.40, slope = 0.43 ms/a.u.).18F-NaF PET-MR imaging enables detection of increased subchondral bone metabolism in ACL-reconstructed knees and may serve as an important marker of early osteoarthritis (OA) progression. Spatial relationships observed between early OA changes across bone and cartilage support the need to study whole-joint disease mechanisms in OA.

  View details for PubMedID 29656143

• Comparison Between Different PET and CT-Based Imaging Interpretation Criteria at Interim Imaging in Patients With Diffuse Large B-Cell Lymphoma CLINICAL NUCLEAR MEDICINE Baratto, L., Davidzon, G. A., Moghbel, M., Hatami, N., Iagaru, A., Mittra, E. S. 2018; 43 (1): 1–8

  Abstract

  To evaluate the predictive value of interim PET (iPET) in diffuse large B-cell lymphoma (DLBCL) using 5 different imaging interpretation criteria: Deauville 5-point scale criteria, International Harmonization Project (IHP) criteria, Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, European Organization for Research and Treatment of Cancer, and PET Response Criteria in Solid Tumors (PERCIST) 1.0.We retrospectively reviewed records from 38 patients with DLBCL who underwent baseline and iPET at our institution. Imaging was interpreted according to the previously mentioned criteria. Results were correlated with end-of-treatment response, based on reports at the end of treatment radiological examinations, overall survival (OS), and progression-free survival (PFS) to assess and compare the predictive value of iPET according to each criterion. We also evaluated the concordance between different criteria.The Deauville and PERCIST criteria were the most reliable for predicting end-of-treatment response, reporting an accuracy of 81.6%. They also correlated with OS and PFS (P = 0.0004 and P = 0.0001, and P = 0.0007 and P = 0.0002, for Deauville and PERCIST, respectively). Interim PET according to European Organization for Research and Treatment of Cancer also predicted the end-of-treatment response with an accuracy of 73.7% and had a significant correlation with OS (P = 0.007) and PFS (P = 0.007). In contrast, the IHP criteria and RECIST did not predict outcomes: the accuracy for end-of-treatment response was 34.2% and 36.8%, respectively, with no significant correlation with OS or PFS (P = 0.182 and P = 0.357, and P = 0.341 and P = 0.215, for OS and PFS, respectively).The predictive value of iPET in DLBCL patients is most reliable using the Deauville and PERCIST criteria. Criteria that rely on anatomical characteristics, namely, RECIST and IHP criteria, are less accurate in predicting patient outcomes in DLBCL.

  View details for DOI 10.1097/RLU.0000000000001880

  View details for Web of Science ID 000418319900001

  View details for PubMedID 29076913

• Standard OSEM vs. regularized PET image reconstruction: qualitative and quantitative comparison using phantom data and various clinical radiopharmaceuticals AMERICAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Lantos, J., Mittra, E. S., Levin, C. S., Iagaru, A. 2018; 8 (2): 110–18

  Abstract

  We investigated the block sequential regularized expectation maximization (BSREM) algorithm. ACR phantom measurements with different count statistics and 60 PET/CT research scans from the GE Discovery 600 and 690 scanners were reconstructed using BSREM and the standard-of-care OSEM algorithm. Hot concentration recovery and cold contrast recovery were measured from the phantom data. Two experienced nuclear medicine physicians reviewed the clinical images blindly. Liver SNR liver and SUVmax of the smallest lesion detected in each patient were also measured. The relationship between the maximum and mean hot concentration recovery remained monotonic below 1.5 maximum concentration recovery. The mean cold contrast recovery remained stable even for decreasing statistics with a highest absolute difference of 4% in air and 2% in bone for each reconstruction method. The D600 images resulted in an average 30% higher SNR than the D690 data for BSREM; there was no difference in SNR results between the two scanners with OSEM. The small lesion SUVmax values on the BSREM images with β of 250, 350 and 450, respectively were on average 80%, 60% and 43% (D690) and 42%, 29%, and 21% (D600) higher than in the case of OSEM. In conclusion, BSREM can outperform OSEM in terms of contrast recovery and organ uniformity over a range of PET tracers, but a task dependent regularization strength parameter (beta) selection may be necessary. To avoid image noise and artifacts, our results suggest that using higher beta values (at least 350) may be appropriate, especially if the data has low count statistics.

  View details for PubMedID 29755844

  View details for PubMedCentralID PMC5944826

• Anaplastic Thyroid Cancer With Extensive Skeletal Muscle Metastases on 18F-FDG PET/CT. Clinical nuclear medicine Yurkiewicz, I. R., Ganjoo, K. N., Iagaru, A. n. 2018

  Abstract

  A 61-year-old woman with newly diagnosed anaplastic thyroid cancer and known metastases to the brain, lungs, and adrenal glands complained of groin muscle pain. F-FDG PET/CT was performed to assess for extent of disease and showed extensive hypermetabolic lesions throughout the skeletal musculature concerning for metastatic disease. As this would be a very rare presentation for anaplastic thyroid carcinoma, a biopsy of the left gluteal muscle was conducted. Pathology demonstrated anaplastic thyroid carcinoma, metastatic to skeletal muscle.

  View details for PubMedID 29356736

• Incidental extra-cardiac findings on (NH3)-N-13 myocardial perfusion PET/CT JOURNAL OF NUCLEAR CARDIOLOGY Iagaru, A. 2017; 24 (6): 1869–70

  View details for PubMedID 28390040

• Ga-68-PSMA-11 PET/CT in Newly Diagnosed Carcinoma of the Prostate: Correlation of Intraprostatic PSMA Uptake with Several Clinical Parameters JOURNAL OF NUCLEAR MEDICINE Koerber, S. A., Utzinger, M. T., Kratochwil, C., Kesch, C., Haefner, M. F., Katayama, S., Mier, W., Iagaru, A. H., Herfarth, K., Haberkorn, U., Debus, J., Giesel, F. L. 2017; 58 (12): 1943–48

  Abstract

  68Ga-prostate-specific membrane antigen (PSMA) PET/CT is a promising diagnostic tool for patients with prostate cancer. Our study evaluates SUVs in benign prostate tissue and malignant, intraprostatic tumor lesions and correlates results with several clinical parameters. Methods: One hundred four men with newly diagnosed prostate carcinoma and no previous therapy were included in this study. SUVmax was measured and correlated with biopsy findings and MRI. Afterward, data were compared with current prostate-specific antigen (PSA) values, Gleason score (GS), and d'Amico risk classification. Results: In this investigation a mean SUVmax of 1.88 ± 0.44 in healthy prostate tissue compared with 10.77 ± 8.45 in malignant prostate lesions (P < 0.001) was observed. Patients with higher PSA, higher GS, and higher d'Amico risk score had statistically significant higher PSMA uptake on PET/CT (P < 0.001 each). Conclusion: PSMA PET/CT is well suited for detecting the intraprostatic malignant lesion in patients with newly diagnosed prostate cancer. Our findings indicate a significant correlation of PSMA uptake with PSA, GS, and risk classification according to the d'Amico scale.

  View details for DOI 10.2967/jnumed.117.190314

  View details for Web of Science ID 000416804900022

  View details for PubMedID 28619734

• Carcinoid Syndrome Complicating a Pancreatic Neuroendocrine Tumor A Case Report PANCREAS Gerson, J. N., Witteles, R. M., Chang, D. T., Beygui, R. E., Iagaru, A. H., Kunz, P. L. 2017; 46 (10): 1381–85

  Abstract

  Neuroendocrine tumors (NETs) comprise a heterogeneous group of neoplasms. These tumors can produce a wide variety of hormones that can lead to syndromes of hormone excess, such as carcinoid syndrome. We present the case of a 47-year-old man who presented with right upper quadrant abdominal pain and emesis. He was found to have metastatic pancreatic NET and was treated with systemic chemotherapy. He subsequently developed dyspnea on exertion and was found to have severe right-sided heart disease secondary to elevated levels of serum serotonin. He was successfully treated with surgical tricuspid and pulmonic valve replacement. True carcinoid syndrome with pancreatic NETs is rare, but, as a treatable complication of the disease, is an important entity for which oncologists should be familiar.

  View details for PubMedID 29040196

• Semiquantitative Assessment of F-18-FDG Uptake in the Normal Skeleton: Comparison Between PET/CT and Time-of-Flight Simultaneous PET/MRI AMERICAN JOURNAL OF ROENTGENOLOGY Minamimoto, R., Xu, G., Jamali, M., Holley, D., Barkhodari, A., Zaharchuk, G., lagaru, A. 2017; 209 (5): 1136–42

  Abstract

  Differences in the attenuation correction methods used in PET/CT scanners versus the newly introduced whole-body simultaneous PET/MRI reportedly result in differences in standardized uptake values (SUVs) in the normal skeleton. The aim of the study was to compare the semiquantitative FDG uptake in the normal skeleton using time-of-flight (TOF) PET/MRI versus PET/CT with and without TOF.Participants received a single FDG injection and underwent non-TOF and TOF PET/CT (n = 23) or non-TOF PET/CT and TOF PET/MRI (n = 50). Mean SUV (SUVmean) and maximum SUV (SUVmax) were measured from all PET scans for nine normal regions of the skeleton. Pearson correlation coefficients (r) were used to evaluate the SUVmax and SUVmean of normal skeleton between non-TOF and TOF PET/CT, as well as between non-TOF PET/CT and TOF PET/MRI. In addition, percentage differences in SUVmax and SUVmean of the normal skeleton between non-TOF and TOF PET/CT and between non-TOF PET/CT and TOF PET/MRI were evaluated.The SUVmax and SUVmean in the normal skeleton significantly increased between non-TOF and TOF PET/CT, but they significantly decreased between non-TOF PET/CT and TOF PET/MRI. The SUVmax and SUVmean in normal skeleton showed good correlation between non-TOF PET/CT and TOF PET/MRI (SUVmax, r = 0.88; SUVmean, r = 0.91) and showed a similar trend between non-TOF and TOF PET/CT (SUVmax, r = 0.88; SUVmean, r = 0.94).In the normal skeleton, SUVmax and SUVmean showed high correlations between PET/MRI and PET/CT. The MRI attenuation correction used in TOF PET/MRI provides reliable semiquantitative measurements in the normal skeleton.

  View details for PubMedID 28777652

• Dual-Integrin alpha(v)beta(3)-and Gastrin-Releasing Peptide Receptor-Targeting PET Radiotracer (Ga-68-BBN-RGD) JOURNAL OF NUCLEAR MEDICINE Iagaru, A. 2017; 58 (10): 1706

  View details for PubMedID 28280224

• Will GRPR Compete with PSMA as a Target in Prostate Cancer? Journal of nuclear medicine : official publication, Society of Nuclear Medicine Iagaru, A. 2017

  View details for PubMedID 28970333

• Clinical evaluation of TOF versus non-TOF on PET artifacts in simultaneous PET/MR: a dual centre experience. European journal of nuclear medicine and molecular imaging Ter Voert, E. E., Veit-Haibach, P., Ahn, S., Wiesinger, F., Khalighi, M. M., Levin, C. S., Iagaru, A. H., Zaharchuk, G., Huellner, M., Delso, G. 2017; 44 (7): 1223-1233

  Abstract

  Our objective was to determine clinically the value of time-of-flight (TOF) information in reducing PET artifacts and improving PET image quality and accuracy in simultaneous TOF PET/MR scanning.A total 65 patients who underwent a comparative scan in a simultaneous TOF PET/MR scanner were included. TOF and non-TOF PET images were reconstructed, clinically examined, compared and scored. PET imaging artifacts were categorized as large or small implant-related artifacts, as dental implant-related artifacts, and as implant-unrelated artifacts. Differences in image quality, especially those related to (implant) artifacts, were assessed using a scale ranging from 0 (no artifact) to 4 (severe artifact).A total of 87 image artifacts were found and evaluated. Four patients had large and eight patients small implant-related artifacts, 27 patients had dental implants/fillings, and 48 patients had implant-unrelated artifacts. The average score was 1.14 ± 0.82 for non-TOF PET images and 0.53 ± 0.66 for TOF images (p < 0.01) indicating that artifacts were less noticeable when TOF information was included.Our study indicates that PET image artifacts are significantly mitigated with integration of TOF information in simultaneous PET/MR. The impact is predominantly seen in patients with significant artifacts due to metal implants.

  View details for DOI 10.1007/s00259-017-3619-2

  View details for PubMedID 28124091

• Initial Experience With Simultaneous 18F-FDG PET/MRI in the Evaluation of Cardiac Sarcoidosis and Myocarditis. Clinical nuclear medicine Hanneman, K., Kadoch, M., Guo, H. H., Jamali, M., Quon, A., Iagaru, A., Herfkens, R. 2017; 42 (7): e328-e334

  Abstract

  The purpose of this study was to compare combined PET/MRI with PET/CT and cardiac MRI in the evaluation of cardiac sarcoidosis and myocarditis.Ten patients (4 men and 6 women; 56.1 ± 9.6 years old) were prospectively enrolled for evaluation of suspected cardiac sarcoidosis or myocarditis. Written informed consent was obtained. Following administration of 9.9 ± 0.9 mCi F-FDG, patients underwent standard cardiac PET/CT followed by combined PET/MRI using a simultaneous 3-T scanner. Cardiac MRI sequences included ECG-triggered cine SSFP, T2-weighted, and late gadolinium-enhanced imaging. Myocardial involvement was assessed with separate analysis of combined PET/MRI, PET/CT, and cardiac MRI data using dedicated postprocessing software. Estimates of radiation dose were derived from the applied doses of F-FDG and CT protocol parameters.Imaging was acquired with a delay from F-FDG injection of 90.2 ± 27.4 minutes for PET/CT and 207.7 ± 40.3 minutes for PET/MRI. Total scan time for PET/MRI was significantly longer than for PET/CT (81.4 ± 14.8 vs 12.0 minutes, P < 0.001). Total effective radiation dose was significantly lower for PET/MRI compared with PET/CT (6.9 ± 0.6 vs 8.2 ± 1.1 mSv, P = 0.007). There was no significant difference in the number of positive cases identified between combined PET/MRI (n = 10 [100%]), PET/CT (n = 6 [60%]), and cardiac MRI (n = 8 [80%]), P = 0.091.Simultaneous cardiac PET/MRI is feasible in the evaluation of cardiac sarcoidosis and myocarditis achieving diagnostic image quality.

  View details for DOI 10.1097/RLU.0000000000001669

  View details for PubMedID 28418949

• American College of Radiology and Society of Nuclear Medicine and Molecular Imaging Joint Credentialing Statement for PET/MR Imaging: Body. Journal of nuclear medicine Subramaniam, R. M., Jadvar, H., Colletti, P. M., Guimaraes, A., Gullapali, R., Iagaru, A. H., McConathy, J., Meltzer, C. C., Nadel, H., Noto, R. B., Packard, A. B., Rohren, E., Oates, M. E. 2017

  Abstract

  This joint statement is intended to guide credentialing bodies that privilege physicians to oversee the performance of and participation in the interpretation of PET/MR imaging in adult and pediatric patients in the United States.

  View details for DOI 10.2967/jnumed.117.193524

  View details for PubMedID 28473601

• Intragastric meal distribution during routine gastric emptying scintigraphy: Validation of visual qualitative and semi-automated quantitative analysis Yu, D., Orthey, P., Ramsey, F., Bennett, P., Diaz, J., Fragomeni, R., Iagaru, A., Parkman, H., Maurer, A. SOC NUCLEAR MEDICINE INC. 2017

  View details for Web of Science ID 000404949901185

• SiPM PET/CT vs. Standard PET/CT: A Pilot Study Comparing Semi-Quantitative Measurements in Normal Tissues and Lesions Baratto, L., Park, S., Hatami, N., Davidzon, G., Srinivas, S., Gambhir, S., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2017

  View details for Web of Science ID 000404949902041

• Imaging Patients with Breast and Prostate Cancers Using Combined F-18 NaF/F-18 FDG and TOF simultaneous PET/MRI Sonni, I., Minamimoto, R., Taviani, V., Hatami, N., Gambhir, S., Vasanawala, S., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2017

  View details for Web of Science ID 000404949903155

• Initial Experience with a SiPM-based PET/CT Scanner: Influence of Acquisition Time on Image Quality Sonni, I., Park, S., Baratto, L., Hatami, N., Davidzon, G., Srinivas, S., Gambhir, S., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2017

  View details for Web of Science ID 000404949906160

• Ga-68 PSMA 11 PET/MRI in Patients with Newly Diagnosed Intermediate and High-Risk Prostate Cancers Zacharias, C., Harrison, C., Ghanouni, P., Sonn, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2017

  View details for Web of Science ID 000404949902137

• Imaging of Prostate Cancer Using Gallium-68-Labeled Bombesin. PET clinics Sonni, I., Baratto, L., Iagaru, A. 2017; 12 (2): 159-171

  Abstract

  Nuclear medicine can play an important role in evaluating prostate cancer combining anatomical and functional information with hybrid techniques. Various PET radiopharmaceuticals have been used for targeting specific biological markers in prostate cancer. Research is ideally oriented towards the development of radiopharmaceuticals targeting antigens overexpressed in prostate cancer, as opposed to normal prostate tissue. In this regard, gastrin-releasing peptide receptors (GRPR) are excellent candidates. Bombesin analogues targeting the GRPR have been investigated. Gallium-68 ((68)Ga) is an interesting PET radioisotope due to several advantages, such as availability, ease of radiochemistry, half-life, and costs. The focus of this review is on (68)Ga-labeled bombesin analogues in prostate cancer.

  View details for DOI 10.1016/j.cpet.2016.11.003

  View details for PubMedID 28267450

• Assessment of skeletal tumour burden on F-18-NaF PET/CT using a new quantitative method NUCLEAR MEDICINE COMMUNICATIONS Lapa, P., Marques, M., Costa, G., Iagaru, A., de Lima, J. P. 2017; 38 (4): 325-332

  Abstract

  The purpose of this study was to test a method of quantifying skeletal tumour burden with F-NaF PET/CT.We retrospectively reviewed the charts of 117 patients who underwent F-NaF PET/CT for the detection of bone metastases, 68 women and 49 men, 16-82 years old (mean±SD: 62.9±10.7 years). Mean standardized uptake values (SUVmean) were measured in five anatomic sites to evaluate normal skeleton activity. The influence of sex and age was investigated. Skeletal tumour burden was calculated in 69 exams positive for bone metastases using volumetric data and SUVmean values. Intraobserver and interobserver reproducibility was tested. In 10 patients with breast cancer, skeletal tumour burden in pretreatment and post-treatment F-NaF PET/CT was compared with tumour marker and clinical evolution.The range of normal skeleton SUVmean for the 410 volume of interests analysed was 2.2-5.9 (mean±SD: 4.4±1.5). A threshold of 10 was chosen to exclude F-NaF normal skeleton uptake. An inverse relationship was found between normal skeleton SUVmean and age (r=-0.237; P=0.032). Our results show excellent intraobserver and interobserver reproducibility, with intraclass correlation values of 0.995 and 0.997, respectively. The percentage change in the skeletal tumour burden in response to therapy shows a moderate direct correlation with the percentage variation of the tumour marker (r=0.668; P=0.035).The methodology that we used to quantify skeletal tumour burden is easy to perform, highly reproducible and allows for the evaluation of bone tumour response to therapy in a subgroup of breast cancer patients. The possibility of skeletal tumour burden quantification is another advantage of F-NaF PET/CT over the visual and subjective interpretation of bone scintigraphy.

  View details for DOI 10.1097/MNM.0000000000000654

  View details for Web of Science ID 000398205600008

• Cisplatin and Etoposide or Temozolomide and Capecitabine in Treating Patients With Neuroendocrine Carcinoma of the Gastrointestinal Tract or Pancreas That Is Metastatic or Cannot Be Removed by Surgery Eads, J. R., Catalano, P., Fisher, G. A., Klimstra, D., Zhang, Z., Rubin, D., Iagaru, A., Wong, T. Z., O'Dwyer, P. LIPPINCOTT WILLIAMS & WILKINS. 2017: 451

  View details for Web of Science ID 000394448600112

• Assessment of skeletal tumour burden on 18F-NaF PET/CT using a new quantitative method. Nuclear medicine communications Lapa, P., Marques, M., Costa, G., Iagaru, A., Pedroso de Lima, J. 2017

  Abstract

  The purpose of this study was to test a method of quantifying skeletal tumour burden with F-NaF PET/CT.We retrospectively reviewed the charts of 117 patients who underwent F-NaF PET/CT for the detection of bone metastases, 68 women and 49 men, 16-82 years old (mean±SD: 62.9±10.7 years). Mean standardized uptake values (SUVmean) were measured in five anatomic sites to evaluate normal skeleton activity. The influence of sex and age was investigated. Skeletal tumour burden was calculated in 69 exams positive for bone metastases using volumetric data and SUVmean values. Intraobserver and interobserver reproducibility was tested. In 10 patients with breast cancer, skeletal tumour burden in pretreatment and post-treatment F-NaF PET/CT was compared with tumour marker and clinical evolution.The range of normal skeleton SUVmean for the 410 volume of interests analysed was 2.2-5.9 (mean±SD: 4.4±1.5). A threshold of 10 was chosen to exclude F-NaF normal skeleton uptake. An inverse relationship was found between normal skeleton SUVmean and age (r=-0.237; P=0.032). Our results show excellent intraobserver and interobserver reproducibility, with intraclass correlation values of 0.995 and 0.997, respectively. The percentage change in the skeletal tumour burden in response to therapy shows a moderate direct correlation with the percentage variation of the tumour marker (r=0.668; P=0.035).The methodology that we used to quantify skeletal tumour burden is easy to perform, highly reproducible and allows for the evaluation of bone tumour response to therapy in a subgroup of breast cancer patients. The possibility of skeletal tumour burden quantification is another advantage of F-NaF PET/CT over the visual and subjective interpretation of bone scintigraphy.

  View details for DOI 10.1097/MNM.0000000000000654

  View details for PubMedID 28230714

• Conspicuity of Malignant Lesions on PET/CT and Simultaneous Time-Of-Flight PET/MRI PLOS ONE Minamimoto, R., Iagaru, A., Jamali, M., Holley, D., Barkhodari, A., Vasanawala, S., Zaharchuk, G. 2017; 12 (1)

  Abstract

  To compare the conspicuity of malignant lesions between FDG PET/CT and a new simultaneous, time-of-flight (TOF) enabled PET/MRI scanner.All patients underwent a single-injection of FDG, followed by a dual imaging protocol consisting of PET/CT followed by TOF PET/MRI. PET/CT and PET/MRI images were evaluated by two readers independently for areas of FDG uptake compatible with malignancy, and then categorized into 5 groups (1: PET/MRI and PET/CT positive; 2: PET/MRI positive, PET/CT positive in retrospect; 3: PET/CT positive, PET/MRI positive in retrospect; 4: PET/MRI positive, PET/CT negative; 5: PET/MRI negative, PET/CT positive) by consensus. Patients with no lesions on either study or greater than 10 lesions based on either modality were excluded from the study.Fifty-two patients (mean±SD age: 58±14 years) underwent the dual imaging protocol; of these, 29 patients with a total of 93 FDG-avid lesions met the inclusion criteria. The majority of lesions (56%) were recorded prospectively in the same location on PET/CT and PET/MRI. About an equal small fraction of lesions were seen on PET/CT but only retrospectively on PET/MRI (9%) and vice versa (12%). More lesions were identified only on PET/MRI but not on PET/CT, even in retrospect (96% vs. 81%, respectively; p = 0.003). Discrepant lesions had lower maximum standardized uptake value (SUVmax) than concordant lesions on both modalities (p<0.001).While most lesions were identified prospectively on both modalities, significantly more lesions were identified with PET/MRI than with PET/CT.

  View details for DOI 10.1371/journal.pone.0167262

  View details for Web of Science ID 000392381100001

  View details for PubMedID 28103230

  View details for PubMedCentralID PMC5245859

• 18F-FDG silicon photomultiplier PET/CT: A pilot study comparing semi-quantitative measurements with standard PET/CT. PloS one Baratto, L., Park, S. Y., Hatami, N., Davidzon, G., Srinivas, S., Gambhir, S. S., Iagaru, A. 2017; 12 (6)

  Abstract

  To evaluate if the new Discovery Molecular Insights (DMI) PET/CT scanner provides equivalent results compared to the standard of care PET/CT scanners (GE Discovery 600 or GE Discovery 690) used in our clinic and to explore any possible differences in semi-quantitative measurements.The local Institutional Review Board approved the protocol and written informed consent was obtained from each patient. Between September and November 2016, 50 patients underwent a single 18F-FDG injection and two scans: the clinical standard PET/CT followed immediately by the DMI PET/CT scan. We measured SUVmax and SUVmean of different background organs and up to four lesions per patient from data acquired using both scanners.DMI PET/CT identified all the 107 lesions detected by standard PET/CT scanners, as well as additional 37 areas of focal increased 18F-FDG uptake. The SUVmax values for all 107 lesions ranged 1.2 to 14.6 (mean ± SD: 2.8 ± 2.8), higher on DMI PET/CT compared with standard of care PET/CT. The mean lesion:aortic arch SUVmax ratio and mean lesion:liver SUVmax ratio were 0.2-15.2 (mean ± SD: 3.2 ± 2.6) and 0.2-8.5 (mean ± SD: 1.9 ± 1.4) respectively, higher on DMI PET/CT than standard PET/CT. These differences were statistically significant (P value < 0.0001) and not correlated to the delay in acquisition of DMI PET data (P < 0.0001).Our study shows high performance of the new DMI PET/CT scanner. This may have a significant role in diagnosing and staging disease, as well as for assessing and monitoring responses to therapies.

  View details for DOI 10.1371/journal.pone.0178936

  View details for PubMedID 28582472

• Prospective Evaluation of 68Ga-RM2 PET/MRI in Patients with Biochemical Recurrence of Prostate Cancer and Negative Conventional Imaging. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Minamimoto, R. n., Sonni, I. n., Hancock, S. n., Vasanawala, S. n., Loening, A. n., Gambhir, S. S., Iagaru, A. n. 2017

  Abstract

  Purpose:68Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (68Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptors (GRPr). GRPr proteins are highly overexpressed in several human tumors, including prostate cancer. We present data from the use of 68Ga-RM2 in patients with biochemical recurrence (BCR) of prostate cancer (PC) and negative conventional imaging (CI). Methods: We enrolled 32 men with BCR PC, 59-83 year-old (mean±standard deviation (SD): 68.7±6.4). Imaging started at 40-69 minutes (mean±SD: 50.5±6.8) after injection of 133.2-151.7 MBq (mean±SD: 140.6±7.4) of 68Ga-RM2 using a time-of-flight (TOF)-enabled simultaneous positron emission tomography (PET) / magnetic resonance imaging (MRI) scanner. T1-weighted (T1w), T2-weighted (T2w) and diffusion-weighted images (DWI) were acquired. Results: All patients had rising prostate specific antigen (PSA) (range: 0.3-119.0 ng/mL; mean±SD: 10.1 ± 21.3) and negative CI (CT or MRI, and 99mTc MDP bone scan) prior to enrollment. The observed 68Ga-RM2 PET detection rate was 71.8%. 68Ga-RM2 PET identified recurrent prostate cancer in 23 of the 32 participants, while the simultaneous MRI scan identified findings compatible with recurrent prostate cancer in 11 of the 32 patients. PSA velocity (PSAv) values were 0.32±0.59 ng/ml/year (range: 0.04-1.9) in patients with negative PET scans and 2.51±2.16 ng/ml/year (range: 0.13-8.68) in patients with positive PET scans (P: 0.006). Conclusion:68Ga-RM2 PET can be used for assessment of GRPr expression in patients with BCR PC. High uptake in multiple areas compatible with cancer lesions suggests that 68Ga-RM2 is a promising PET radiopharmaceutical for localization of disease in participants with BCR PC and negative CI.

  View details for PubMedID 29084827

• Relative value of three whole-body MR approaches for PET-MR, including gadofosveset-enhanced MR, in comparison to PET-CT. Clinical imaging Obara, P. n., Loening, A. n., Taviani, V. n., Iagaru, A. n., Hargreaves, B. A., Vasanawala, S. n. 2017; 48: 62–68

  Abstract

  Evaluate MR protocol for PET-MR including coronal DWI (cDWI), fat-suppressed T2 (T2w), and gadofosveset-enhanced T1 (CE).18 patients underwent same-day PET-CT and PET-MR. Image quality and performance of each sequence, and combination of all three sequences, was evaluated with respect to PET-CT.Lesion conspicuity was best on cDWI, while delineation was best on CE. Considering all three sequences combined, both readers showed good sensitivity and specificity (>80%). Relative sensitivity was highest on CE and lowest on T2w.Whole-body MR performed well in detecting malignant lesions compared to PET-CT. CE showed overall highest performance.

  View details for PubMedID 29031209

• Treatment and Outcomes in Classical Hodgkin Lymphoma Post-Transplant Lymphoproliferative Disorder in Children Twist, C., Hiniker, S., Gratzinger, D., Iagaru, A., Link, M., Donaldson, S. WILEY-BLACKWELL. 2016: S180

  View details for Web of Science ID 000384818801126

• Improvements in PET Image Quality in Time of Flight (TOF) Simultaneous PET/MRI. Molecular imaging and biology Minamimoto, R., Levin, C., Jamali, M., Holley, D., Barkhodari, A., Zaharchuk, G., Iagaru, A. 2016; 18 (5): 776-781

  Abstract

  An integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) scanner with time of flight (TOF) technology is now available for clinical use. The aim of this study is to evaluate the potential of TOF PET in PET/MRI to reduce artifacts in PET images when compared to non-TOF PET/MRI, TOF PET/X-ray computed tomography (CT), and non-TOF PET/CT.All patients underwent a single 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) injection, followed first by PET/CT, and subsequently by PET/MRI. PET/CT exams were requested as standard-of-care for oncological indications. Using the PET acquisitions datasets, 4 series of images (TOF PET/CT, non-TOF PET/CT, TOF PET/MRI, and non-TOF PET/MRI) were reconstructed. These image series were visually evaluated for: (1) dental metal artifacts, (2) breathing artifacts, and (3) pelvic artifacts due to scatter correction errors from high bladder [(18)F]FDG concentration. PET image quality was assessed by a 3-point scale (1-clinically significant artifact, 2-non clinically significant artifact, and 3-no artifact).Twenty-five patients (mean ± SD age: 56 ± 13 years old; female: 10, male: 15) were enrolled. TOF PET/MRI, non-TOF PET/MRI, TOF PET/CT, and non-TOF PET/CT scores 2.8, 2.5, 2.4, and 2.3, respectively for the presence of dental artifacts, 2.8, 2.5, 2.2, and 1.9, respectively, for the presence of breathing artifacts, and 2.7, 1.7, 2.0, and 1.3, respectively, for the presence of pelvic artifacts TOF PET/MRI images showed the highest image quality scores among the 4 datasets of PET images.The superior timing resolution and resulting TOF capability of the new PET/MRI scanner improved PET image quality in this cohort by reducing artifacts compared to non-TOF PET/MRI, TOF PET/CT, and non-TOF PET/CT.

  View details for DOI 10.1007/s11307-016-0939-8

  View details for PubMedID 26884058

• Imaging patients with breast and prostate cancers using combined 18F-NaF/18F-FDG and TOF simultaneous PET/MRI Sonni, I., Minamimoto, R., Taviani, V., Loening, A., Gambhir, S. S., Vasanawala, S., Iagaru, A. SPRINGER. 2016: S152

  View details for Web of Science ID 000391801600371

• Ga68 RM2 PET/MRI Evaluation of Gastrin-Releasing Peptide Receptor Status in Patients with Biochemically Recurrent Prostate Cancer and Negative Conventional Imaging Iagaru, A., Sonni, I., Minamimoto, R., Loening, A., Vasanawala, S. SPRINGER. 2016: S28

  View details for Web of Science ID 000391801600047

• Bone-Targeted Imaging and Radionuclide Therapy in Prostate Cancer JOURNAL OF NUCLEAR MEDICINE Iagaru, A. H., Mittra, E., Colletti, P. M., Jadvar, H. 2016; 57: 19S-24S

  Abstract

  Although selective metabolic and receptor-based molecular agents will surely be included in the future of prostate cancer diagnosis and therapy, currently available inorganic compounds-such as (18)F-NaF for the diagnosis of bony disease and (223)RaCl2 for the therapy of bone metastases-were recently shown to be superior to standard (99m)Tc-phosphonates for diagnosis and (153)Sm-ethylenediaminetetramethylene phosphonate or (89)SrCl2 for therapy. The advantages of (18)F-NaF include improved lesion detection and, when used in combination with CT, improved diagnostic confidence and specificity. In addition to being the first approved α-emitter, (223)RaCl2 is the first radiopharmaceutical to show an increase in overall survival, a decrease in skeletal events, palliation of bone pain, and a low profile of adverse reactions (which are mild and manageable). The management of metastatic bone disease with (223)RaCl2 is uniquely satisfying, as patients can be monitored directly during their monthly treatment visits.

  View details for DOI 10.2967/jnumed.115.170746

  View details for Web of Science ID 000384962100005

  View details for PubMedID 27694165

• Bombesin-Targeted PET of Prostate Cancer JOURNAL OF NUCLEAR MEDICINE Mansi, R., Minamimoto, R., Macke, H., Iagaru, A. H. 2016; 57: 67S-72S

  Abstract

  Imaging plays an important role in prostate cancer (PC), including accurate evaluation of the extent of disease, assessment of sites of recurrent disease, and monitoring of response to treatment. Molecular imaging techniques are among the novel developments related to the imaging of PC, and various SPECT and PET radiopharmaceuticals are now available in clinical trials or commercially. Here we describe the preclinical and clinical use of gastrin-releasing peptide receptors as targets for the imaging of PC, with a focus on the development of PET tracers for the imaging of gastrin-releasing peptide receptor-positive tumors.

  View details for DOI 10.2967/jnumed.115.170977

  View details for Web of Science ID 000384962100013

  View details for PubMedID 27694175

• Clinical significance of extraskeletal computed tomography findings on 18F-NaF PET/CT performed for osseous metastatic disease evaluation. Nuclear medicine communications Guo, H. H., Moradi, F., Iagaru, A. 2016; 37 (9): 975-982

  Abstract

  Extraskeletal findings detected on whole-body low-dose unenhanced computed tomography (CT) as a part of F-NaF PET/CT scans can be numerous and present challenges for further management. Here, we investigate the frequency and clinical significance of extraskeletal findings among 130 consecutive patients undergoing F-NaF PET/CT for osseous metastatic disease.F-NaF PET/CT performed on 130 patients (101 men and 29 women; mean age: 61.4 years) with biopsy-proven malignancies were reviewed independently. Incidental soft tissue findings detected on unenhanced low-dose CT portions of the scans were compiled and categorized by clinical significance.A total of 275 incidental extraskeletal CT findings were observed in 114 out of 130 patients (87.7%). Seven patients (5.4%) showed clinically significant findings. One patient developed new lung nodules that were resected and proven to be metastases. Two patients showed new hypodense hepatic lesions that were highly suspicious for liver metastases. One patient with prostate cancer was found to have previously unknown retroperitoneal lymphadenopathy. Three patients showed indeterminate renal and adrenal lesions that necessitated further correlative imaging.Although CT indicated a large number of incidental extraskeletal lesions in the majority of patients undergoing F-NaF PET/CT, clinically significant incidental findings requiring further evaluation were relatively infrequently observed in 5.4% of patients. Thus, the low-dose unenhanced CT in F-NaF PET/CT performed for oncologic evaluation may indicate unexpected soft tissue lesions that can impact patient management and therefore should be interpreted by physicians skilled in CT reading, with correlation to available imaging, and familiar with established guidelines for work-up of incidental findings.

  View details for DOI 10.1097/MNM.0000000000000531

  View details for PubMedID 27111100

• Systemic Radioligand Therapy with Lu-177 Labeled Prostate Specific Membrane Antigen Ligand for Imaging and Therapy in Patients with Metastatic Castration Resistant Prostate Cancer EDITORIAL COMMENT JOURNAL OF UROLOGY Iagaru, A. 2016; 196 (2): 390

  View details for DOI 10.1016/j.juro.2016.02.2999

  View details for Web of Science ID 000379266400036

  View details for PubMedID 27207377

• Editorial Comment. The Journal of urology Iagaru, A. 2016; 196 (2): 390

  View details for DOI 10.1016/j.juro.2016.02.2998

  View details for PubMedID 27207378

• Glioblastoma Multiforme Recurrence: An Exploratory Study of (18)F FPPRGD2 PET/CT. Radiology Iagaru, A., Mosci, C., Mittra, E., Zaharchuk, G., Fischbein, N., Harsh, G., Li, G., Nagpal, S., Recht, L., Gambhir, S. S. 2016; 280 (1): 328-?

  View details for DOI 10.1148/radiol.2016164020

  View details for PubMedID 27322985

• PET Imaging Toward Individualized Management of Urologic and Gynecologic Malignancies. PET clinics Sonni, I., Iagaru, A. 2016; 11 (3): 261-272

  Abstract

  Advances in the understanding of cellular and molecular basis of tumor progression have spurred interest in the development of new targeted agents that are changing the therapeutic management of patients with cancer. In parallel to progression in the therapeutic area, new PET radiopharmaceuticals are being developed to guide the use of such targeted therapies. This article aims to give an overview on the role of PET imaging in the individualized management of patients affected by urologic and gynecologic malignancies, focusing on the most promising targets for therapies and for molecular imaging using PET.

  View details for DOI 10.1016/j.cpet.2016.02.007

  View details for PubMedID 27321030

• A Prospective, Matched Comparison Study of SUV Measurements From Time-of-Flight Versus Non-Time-of-Flight PET/CT Scanners CLINICAL NUCLEAR MEDICINE Thompson, H. M., Minamimoto, R., Jamali, M., Barkhodari, A., von Eyben, R., Iagaru, A. 2016; 41 (7): E323-E326

  Abstract

  As quantitative F-FDG PET numbers and pooling of results from different PET/CT scanners become more influential in the management of patients, it becomes imperative that we fully interrogate differences between scanners to fully understand the degree of scanner bias on the statistical power of studies.Participants with body mass index (BMI) greater than 25, scheduled on a time-of-flight (TOF)-capable PET/CT scanner, had a consecutive scan on a non-TOF-capable PET/CT scanner and vice versa. SUVmean in various tissues and SUVmax of malignant lesions were measured from both scans, matched to each subject. Data were analyzed using a mixed-effects model, and statistical significance was determined using equivalence testing, with P < 0.05 being significant.Equivalence was established in all baseline organs, except the cerebellum, matched per patient between scanner types. Mixed-effects method analysis of lesions, repeated between scan types and matched per patient, demonstrated good concordance between scanner types.Patients could be scanned on either a TOF or non-TOF-capable PET/CT scanner without clinical compromise to quantitative SUV measurements.

  View details for DOI 10.1097/RLU.0000000000001170

  View details for Web of Science ID 000377695800002

  View details for PubMedID 26914563

• Pilot prospective evaluation of F-18-FPPRGD(2) PET/CT in patients with cervical and ovarian cancer EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Minamimoto, R., Karam, A., Jamali, M., Barkhodari, A., Gambhir, S. S., Dorigo, O., Iagaru, A. 2016; 43 (6): 1047-1055

  Abstract

  We report the effect of antiangiogenic therapy on the biodistribution of (18)F-FPPRGD2 (a surrogate biomarker of integrin αvβ3 expression), and the potential of (18)F-FPPRGD2 to predict the prognosis in patients with cervical cancer and ovarian cancer in this clinical scenario.Data from six women, age range 30 - 59 years (mean ± SD 44.0 ± 12.5 years), who had undergone a (18)F-FPPRGD2 PET/CT scan and bevacizumab-containing therapy were prospectively collected and analyzed. We compared baseline (18)F-FPPRGD2 and (18)F-FDG uptake in the lesions and tumor-to-background (T/B) ratios. The maximum and mean (18)F-FPPRGD2 standardized uptake values (SUVmax and SUVmean) were recorded for 13 normal organs, as well as in all the identified malignant lesions on the pretreatment scan and the 1-week post-treatment scan. We also measured changes in (18)F-FPPRGD2 uptake from before to 1 week after treatment, and compared them to the changes in (18)F-FDG uptake from before to 6 weeks after treatment. Treatment outcomes were correlated with these changes.The uptake in lesions and T/B ratio of (18)F-FPPRGD2 were lower than those of (18)F-FDG (SUVmax 3.7 ± 1.3 vs. 6.0 ± 1.8, P < 0.001; SUVmean 2.6 ± 0.7 vs. 4.2 ± 1.3, P < 0.001; T/B ratio based on SUVmax 2.4 ± 1.0 vs. 2.6 ± 1.0, P < 0.04; T/B ratio based on SUVmean 1.9 ± 0.6 vs. 2.4 ± 1.0, P < 0.003). One patient did not return for the follow-up scan and in another patient no lesions were identified on the pretreatment scan. (18)F-FPPRGD2 uptake in lesions in the remaining four patients had significantly changed 1 week after treatment (SUVmean 3.3 ± 1.0 vs. 2.7 ± 1.0, P < 0.001), while uptake in all normal tissues analyzed was not affected by treatment. One patient with clinical disease progression had a decrease in lesional (18)F-FPPRGD2 SUVmean of 1.6 % and in (18)F-FDG SUVmean of 9.4 %. Two patients with a clinical complete response to treatment had decreases in lesional (18)F-FPPRGD2 SUVmean of 25.2 % and 25.0 % and in (18)F-FDG SUVmean of 6.1 % and 71.8 %. One patient with a clinical partial response had a decrease in lesional (18)F-FPPRGD2 SUVmean of 7.9 % and in (18)F-FDG SUVmean of 76.4 %.This pilot study showed that (18)F-FPPRGD2 and (18)F-FDG provide independent information about the biology of ovarian and cervical cancers. Bevacizumab-containing therapy does not affect (18)F-FPPRGD2 uptake in normal organs, but does result in statistically significant changes in lesions. In addition, (18)F-FPPRGD2 may have potential for early prediction of response to such treatments. These preliminary findings have to be confirmed in larger studies.

  View details for DOI 10.1007/s00259-015-3263-7

  View details for Web of Science ID 000374972900008

  View details for PubMedID 26611425

• Spectrum of Ga-68-DOTA TATE Uptake in Patients With Neuroendocrine Tumors CLINICAL NUCLEAR MEDICINE Moradi, F., Jamali, M., Barkhodari, A., Schneider, B., Chin, F., Quon, A., Mittra, E. S., Iagaru, A. 2016; 41 (6): E281-E287

  Abstract

  To analyze the biodistribution of Ga-DOTA-TATE in the normal tissues and uptake in benign, indeterminate, and malignant lesions in a population of patients with known neuroendocrine tumors (NET) using semiquantitative standardized uptake values (SUV) measurements.One hundred four consecutively scanned patients (51 men and 53 women; mean age, 56.4 years) with confirmed diagnosis of NET underwent PET/CT 1 hour after administration of Ga-DOTA-TATE. SUVmean, and SUVmax were measured in 37 normal anatomical structures for each patient. Abnormal uptake was divided into benign, indeterminate, and malignant categories based on imaging characteristic, clinical follow-up, and pathology.High physiologic uptake (SUVmax > 7) was observed in spleen, renal parenchyma, adrenal glands, pituitary gland, stomach, and liver (in decreasing order). Moderate uptake (3.5-7) was present in the prostate, jejunum, pancreas, ileum, and salivary glands. Mild uptake (2-3.5) was present in the uterus, colon, thyroid, rectum, and skeleton. A total of 678 lesions (limited to 5 lesions with highest uptake per organ) were included in the analysis, including 127 benign and 54 indeterminate lesions. Uptake was significantly higher in malignant lesions than in benign lesions, but an overlap was noted between the groups.Ga-DOTA TATE uptake in normal and abnormal structures is highly variable in patients with NET. SUV is a useful measure for characterizing benign versus malignant lesions. Anatomical and clinical correlation may be necessary to characterize foci of intermediate uptake.

  View details for DOI 10.1097/RLU.0000000000001100

  View details for Web of Science ID 000376886800003

  View details for PubMedID 26673240

• Pilot Comparison of Ga-68-RM2 PET and Ga-68-PSMA-11 PET in Patients with Biochemically Recurrent Prostate Cancer JOURNAL OF NUCLEAR MEDICINE Minamimoto, R., Hancock, S., Schneider, B., Chin, F. T., Jamali, M., Loening, A., Vasanawala, S., Gambhir, S. S., Iagaru, A. 2016; 57 (4): 557-562

  Abstract

  Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)] ((68)Ga-PSMA-11) is a PET tracer that can detect prostate cancer relapses and metastases by binding to the extracellular domain of PSMA.(68)Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 ((68)Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptors. We present pilot data on the biodistribution of these PET tracers in a small cohort of patients with biochemically recurrent prostate cancer.Seven men (mean age ± SD, 74.3 ± 5.9 y) with biochemically recurrent prostate cancer underwent both(68)Ga-PSMA-11 PET/CT and(68)Ga-RM2 PET/MRI scans. SUVmaxand SUVmeanwere recorded for normal tissues and areas of uptake outside the expected physiologic biodistribution.All patients had a rising level of prostate-specific antigen (mean ± SD, 13.5 ± 11.5) and noncontributory results on conventional imaging.(68)Ga-PSMA-11 had the highest physiologic uptake in the salivary glands and small bowel, with hepatobiliary and renal clearance noted, whereas(68)Ga-RM2 had the highest physiologic uptake in the pancreas, with renal clearance noted. Uptake outside the expected physiologic biodistribution did not significantly differ between(68)Ga-PSMA-11 and(68)Ga-RM2; however,(68)Ga-PSMA-11 localized in a lymph node and seminal vesicle in a patient with no abnormal(68)Ga-RM2 uptake. Abdominal periaortic lymph nodes were more easily visualized by(68)Ga-RM2 in two patients because of lack of interference by radioactivity in the small intestine.(68)Ga-PSMA-11 and(68)Ga-RM2 had distinct biodistributions in this small cohort of patients with biochemically recurrent prostate cancer. Additional work is needed to understand the expression of PSMA and gastrin-releasing peptide receptors in different types of prostate cancer.

  View details for DOI 10.2967/jnumed.115.168393

  View details for PubMedID 26659347

• Evaluation of a new motion correction algorithm in PET/CT: combining the entire acquired PET data to create a single three-dimensional motion-corrected PET/CT image NUCLEAR MEDICINE COMMUNICATIONS Minamimoto, R., Mitsumoto, T., Miyata, Y., Sunaoka, F., Morooka, M., Okasaki, M., Iagaru, A., Kubota, K. 2016; 37 (2): 162-170

  Abstract

  This study evaluated the potential of Q.Freeze algorithm for reducing motion artifacts, in comparison with ungated imaging (UG) and respiratory-gated imaging (RG).Twenty-nine patients with 53 lesions who had undergone RG F-FDG PET/CT were included in this study. Using PET list mode data, five series of PET images [UG, RG, and QF images with an acquisition duration of 3 min (QF3), 5 min (QF5), and 10 min (QF10)] were reconstructed retrospectively. The image quality was evaluated first. Next, quantitative metrics [maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), SD, metabolic tumor volume, signal to noise ratio, or lesion to background ratio] were calculated for the liver, background, and each lesion, and the results were compared across the series.QF10 and QF5 showed better image quality compared with all other images. SUVmax in the liver, background, and lesions was lower with QF10 and QF5 than with the others, but there were no statistically significant differences in SUVmean and the lesion to background ratios. The SD with UG and RG was significantly higher than that with QF5 and QF10. The metabolic tumor volume in QF3 and QF5 was significantly lower than that in UG.The Q.Freeze algorithm can improve the quality of PET imaging compared with RG and UG.

  View details for DOI 10.1097/MNM.0000000000000423

  View details for Web of Science ID 000373508500009

  View details for PubMedID 26513056

• Ga-68-DOTA-Bombesin (Ga-68-RM2 or Ga-68-Bombesin) PET versus Ga-68-PSMA PET: A pilot prospective evaluation in patients with biochemical recurrence of prostate cancer. Iagaru, A., Minamimoto, R., Hancock, S., Mittra, E., Loening, A., Vasanawala, S. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/jco.2016.34.2_suppl.331

  View details for Web of Science ID 000378109100329

• Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies. PloS one Mittra, E. S., Koglin, N., Mosci, C., Kumar, M., Hoehne, A., Keu, K. V., Iagaru, A. H., Mueller, A., Berndt, M., Bullich, S., Friebe, M., Schmitt-Willich, H., Gekeler, V., Fels, L. M., Bacher-Stier, C., Moon, D. H., Chin, F. T., Stephens, A. W., Dinkelborg, L. M., Gambhir, S. S. 2016; 11 (2)

  Abstract

  (S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid (18F-FSPG) is a novel radiopharmaceutical for Positron Emission Tomography (PET) imaging. It is a glutamate analogue that can be used to measure xC- transporter activity. This study was performed to assess the feasibility of 18F-FSPG for imaging orthotopic brain tumors in small animals and the translation of this approach in human subjects with intracranial malignancies.For the small animal study, GS9L glioblastoma cells were implanted into brains of Fischer rats and studied with 18F-FSPG, the 18F-labeled glucose derivative 18F-FDG and with the 18F-labeled amino acid derivative 18F-FET. For the human study, five subjects with either primary or metastatic brain cancer were recruited (mean age 50.4 years). After injection of 300 MBq of 18F-FSPG, 3 whole-body PET/Computed Tomography (CT) scans were obtained and safety parameters were measured. The three subjects with brain metastases also had an 18F-FDG PET/CT scan. Quantitative and qualitative comparison of the scans was performed to assess kinetics, biodistribution, and relative efficacy of the tracers.In the small animals, the orthotopic brain tumors were visualized well with 18F-FSPG. The high tumor uptake of 18F-FSPG in the GS9L model and the absence of background signal led to good tumor visualization with high contrast (tumor/brain ratio: 32.7). 18F-FDG and 18F-FET showed T/B ratios of 1.7 and 2.8, respectively. In the human pilot study, 18F-FSPG was well tolerated and there was similar distribution in all patients. All malignant lesions were positive with 18F-FSPG except for one low-grade primary brain tumor. In the 18F-FSPG-PET-positive tumors a similar T/B ratio was observed as in the animal model.18F-FSPG is a novel PET radiopharmaceutical that demonstrates good uptake in both small animal and human studies of intracranial malignancies. Future studies on larger numbers of subjects and a wider array of brain tumors are planned.ClinicalTrials.gov NCT01186601.

  View details for DOI 10.1371/journal.pone.0148628

  View details for PubMedID 26890637

  View details for PubMedCentralID PMC4758607

• Whole-body simultaneous time-of-flight PET-MRI: early experience with clinical studies. EJNMMI physics Minamimoto, R., Iagaru, A., Jamali, M., Barkodhodari, A., Holley, D., Vasanawala, S., Zaharchuk, G. 2015; 2: A64-?

  View details for DOI 10.1186/2197-7364-2-S1-A64

  View details for PubMedID 26956324

  View details for PubMedCentralID PMC4798693

• Imaging patients with breast and prostate cancers using combined 18F NaF/18F FDG and TOF simultaneous PET/ MRI. EJNMMI physics Iagaru, A., Minamimoto, R., Jamali, M., Barkodhodari, A., Gambhir, S. S., Vasanawala, S. 2015; 2: A65-?

  View details for DOI 10.1186/2197-7364-2-S1-A65

  View details for PubMedID 26956325

  View details for PubMedCentralID PMC4798635

• Prospective Comparison of 99mTc-MDP Scintigraphy, Combined 18F-NaF and 18F-FDG PET/CT, and Whole-Body MRI in Patients with Breast and Prostate Cancer. Journal of nuclear medicine Minamimoto, R., Loening, A., Jamali, M., Barkhodari, A., Mosci, C., Jackson, T., Obara, P., Taviani, V., Gambhir, S. S., Vasanawala, S., Iagaru, A. 2015; 56 (12): 1862-1868

  Abstract

  We prospectively evaluated the combined (18)F-NaF/(18)F-FDG PET/CT in patients with breast and prostate cancers, and compared the results to (99m)Tc MDP bone scintigraphy (BS) and whole-body MRI (WBMRI).30 patients (15 women with breast cancer and 15 men with prostate cancer) referred for standard of care BS were prospectively enrolled in this study. (18)F-NaF/(18)F-FDG PET/CT and WBMRI were performed following BS. WBMRI protocol consisted of both non-contrast enhanced and contrast enhanced sequences. Lesions detected with each test were tabulated and the results were compared.For extra skeletal lesions, (18)F-/(18)F-FDG PET/CT and WBMRI had no statistically significant differences in sensitivity (92.9% vs 92.9%, P = 1.00), PPV (81.3% vs 86.7%, P = 0.68) and accuracy (76.5% vs 82.4%, P = 0.56). However, (18)F-/(18)F-FDG PET/CT showed significantly higher sensitivity and accuracy than WBMRI (96.2% vs 81.4%, P<0.001, 89.8% vs 74.7%, P = 0.01) and BS (96.2% vs 64.6%, P<0.001, 89.8% vs 65.9%, P<0.001) for the detection of skeletal lesions. Overall, (18)F-/(18)F-FDG PET/CT showed higher sensitivity and accuracy than WBMRI (95.7% vs 83.3%, P<0.002, 87.6% vs 76.0%, P< 0.02), but not statistically significant when compared to a combination of WBMRI and BS (95.7% vs 91.6%, P = 0.17, 87.6% vs 83.0%, P = 0.53). (18)F-/(18)F-FDG PET/CT showed no significant difference with a combination of (18)F-/(18)F-FDG PET/CT and WBMRI. No statistically significant differences in PPV were noted among the 3 examinations.The (18)F NaF/(18)F FDG PET/CT is superior to WBMRI and (99m)Tc-MDP scintigraphy for evaluation of skeletal disease extent. Further, (18)F NaF/(18)F FDG PET/CT and WBMRI detected extra-skeletal disease that may change the management of these patients. The (18)F NaF/(18)F FDG PET/CT provide similar diagnostic ability with combination of WBMRI and BS in patients with breast and prostate cancers. Larger cohorts are needed in order to confirm these preliminary findings, ideally using the newly introduced simultaneous PET/MRI scanners.

  View details for DOI 10.2967/jnumed.115.162610

  View details for PubMedID 26405167

• Dynamic brain PET/MR using TOF reconstruction. EJNMMI physics Khalighi, M. M., Delso, G., Tohme, M., Iagaru, A., Zaharchuk, G. 2015; 2: A60-?

  View details for DOI 10.1186/2197-7364-2-S1-A60

  View details for PubMedID 26956320

• The potential of TOF PET-MRI for reducing artifacts in PET images. EJNMMI physics Iagaru, A., Minamimoto, R., Levin, C., Barkhodari, A., Jamali, M., Holley, D., Greg, Z. 2015; 2: A77-?

  View details for DOI 10.1186/2197-7364-2-S1-A77

  View details for PubMedID 26956338

  View details for PubMedCentralID PMC4798707

• Glioblastoma Multiforme Recurrence: An Exploratory Study of F-18 FPPRGD(2) PET/CT1 RADIOLOGY Iagaru, A., Mosci, C., Mittra, E., Zaharchuk, G., Fischbein, N., Harsh, G., Li, G., Nagpal, S., Recht, L., Gambhir, S. S. 2015; 277 (2): 497-506

  Abstract

  Purpose To prospectively evaluate fluorine 18 ((18)F) 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) (FPPRGD2) positron emission tomography (PET) in patients with glioblastoma multiforme (GBM). Materials and Methods The institutional review board approved this HIPAA-compliant protocol. Written informed consent was obtained from each patient. (18)F FPPRGD2 uptake was measured semiquantitatively in the form of maximum standardized uptake values (SUVmax) and uptake volumes before and after treatment with bevacizumab. Vital signs and laboratory results were collected before, during, and after the examinations. A nonparametric version of multivariate analysis of variance was used to assess safety outcome measures simultaneously across time points. A paired two-sample t test was performed to compare SUVmax. Results A total of 17 participants (eight men, nine women; age range, 25-65 years) were enrolled prospectively. (18)F FPPRGD2 PET/computed tomography (CT), (18)F fluorodeoxyglucose (FDG) PET/CT, and brain magnetic resonance (MR) imaging were performed within 3 weeks, prior to the start of bevacizumab therapy. In eight of the 17 patients (47%), (18)F FPPRGD2 PET/CT was repeated 1 week after the start of bevacizumab therapy; six patients (35%) underwent (18)F FPPRGD2 PET/CT a third time 6 weeks after starting bevacizumab therapy. There were no changes in vital signs, electrocardiographic findings, or laboratory values that qualified as adverse events. One patient (6%) had recurrent GBM identified only on (18)F FPPRGD2 PET images, and subsequent MR images enabled confirmation of recurrence. Of the 17 patients, 14 (82%) had recurrent GBM identified on (18)F FPPRGD2 PET and brain MR images, while (18)F FDG PET enabled identification of recurrence in 13 (76%) patients. Two patients (12%) had no recurrent GBM. Conclusion (18)F FPPRGD2 is a safe PET radiopharmaceutical that has increased uptake in GBM lesions. Larger cohorts are required to confirm these preliminary findings. (©) RSNA, 2015 Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.2015141550

  View details for Web of Science ID 000368435100026

• Biodistribution of the (18)F-FPPRGD2 PET radiopharmaceutical in cancer patients: an atlas of SUV measurements. European journal of nuclear medicine and molecular imaging Minamimoto, R., Jamali, M., Barkhodari, A., Mosci, C., Mittra, E., Shen, B., Chin, F., Gambhir, S. S., Iagaru, A. 2015; 42 (12): 1850-1858

  Abstract

  The aim of this study was to investigate the biodistribution of 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) ((18)F-FPPRGD2) in cancer patients and to compare its uptake in malignant lesions with (18)F-FDG uptake.A total of 35 patients (11 men, 24 women, mean age 52.1 ± 10.8 years) were enrolled prospectively and had (18)F-FPPRGD2 PET/CT prior to treatment. Maximum standardized uptake values (SUVmax) and mean SUV (SUVmean) were measured in 23 normal tissues in each patient, as well as in known or suspected cancer lesions. Differences between (18)F-FPPRGD2 uptake and (18)F-FDG uptake were also evaluated in 28 of the 35 patients.Areas of high (18)F-FPPRGD2 accumulation (SUVmax range 8.9 - 94.4, SUVmean range 7.1 - 64.4) included the bladder and kidneys. Moderate uptake (SUVmax range 2.1 - 6.3, SUVmean range 1.1 - 4.5) was found in the choroid plexus, salivary glands, thyroid, liver, spleen, pancreas, small bowel and skeleton. Compared with (18)F-FDG, (18)F-FPPRGD2 showed higher tumor-to-background ratio in brain lesions (13.4 ± 8.5 vs. 1.1 ± 0.5, P < 0.001), but no significant difference in body lesions (3.2 ± 1.9 vs. 4.4 ± 4.2, P = 0.10). There was no significant correlation between the uptake values (SUVmax and SUVmean) for (18)F FPPRGD2 and those for (18)F-FDG.The biodistribution of (18)F-FPPRGD2 in cancer patients is similar to that of other RGD dimer peptides and it is suitable for clinical use. The lack of significant correlation between (18)F-FPPRGD2 and (18)F-FDG uptake confirms that the information provided by each PET tracer is different.

  View details for DOI 10.1007/s00259-015-3096-4

  View details for PubMedID 26062933

• Incorporation of TOF information reduces artifacts in simultaneous TOF PET/MR scanning ter Voert, E., Davison, H., Barbosa, F., Huellner, M., Ahn, S., Wiesinger, F., Levin, C., Iagaru, A., Zaharchuk, G., Delso, G., Veit-Haibach, P. SPRINGER. 2015: S437–S438

  View details for Web of Science ID 000363013202374

• Semi-quantitative assessment of 18F FDG uptake in the normal skeleton using simultaneous PET/MRI: initial comparison to PET/CT in 50 patients Xu, G., Minamimoto, R., Quon, A., Mittra, E., Iagaru, A. SPRINGER. 2015: S18

  View details for Web of Science ID 000363013201019

• Standard OSEM vs. Regularized PET Image Reconstruction: Qualitative and Semi-Quantitative Comparison Iagaru, A., Lantos, J., Mittra, E., Levin, C. SPRINGER. 2015: S354

  View details for Web of Science ID 000363013202204

• F-18-Fluoride PET in the Assessment of Malignant Bone Disease JOURNAL OF NUCLEAR MEDICINE Iagaru, A. 2015; 56 (10): 1476–77

  View details for PubMedID 26294299

• Combined 18F NaF/18F FDG and TOF simultaneous PET/MRI: One-Stop Shop Staging of Patients with Breast and Prostate Cancers Minamimoto, R., Loening, A., Obara, P., Taviani, V., Gambhir, S. S., Vasanawala, S., Iagaru, A. SPRINGER. 2015: S438–S439

  View details for Web of Science ID 000363013202376

• Improvements in PET Image quality from TOF PET/MRI Minamimoto, R., Jamali, M., Barkhodari, A., Holley, D., Zaharchuk, G., Levin, C., Iagaru, A. SPRINGER. 2015: S19

  View details for Web of Science ID 000363013201021

• Combined F-18-NaF and F-18-FDG PET/CT in the Evaluation of Sarcoma Patients CLINICAL NUCLEAR MEDICINE Jackson, T., Mosci, C., von Eyben, R., Mittra, E., Ganjoo, K., Biswal, S., Gambhir, S. S., Iagaru, A. 2015; 40 (9): 720-724

  Abstract

  The combined administration of F-NaF and F-FDG in a single PET/CT scan has the potential to improve patient convenience and cancer detection. Here we report the use of this approach for patients with sarcomas.This is a retrospective review of 21 patients (12 men, 9 women; age, 19-66 years) with biopsy-proven sarcomas who had separate F-NaF PET/CT, F-FDG PET/CT, and combined F-NaF/F-FDG PET/CT scans for evaluation of malignancy. Two board-certified nuclear medicine physicians and 1 board-certified musculoskeletal radiologist were randomly assigned to review the scans. Results were analyzed for sensitivity and specificity, using linear regression and receiver operating characteristics.A total of 13 patients had metastatic disease on F-NaF PET/CT, F-FDG PET/CT, and combined F-NaF/F-FDG PET/CT. Skeletal disease was more extensive on the F-NaF PET/CT scan than on the F-FDG PET/CT in 3 patients, whereas in 1 patient, F-FDG PET/CT showed skeletal disease and the F-NaF PET/CT was negative. Extraskeletal lesions were detected on both F-FDG and combined F-NaF/F-FDG PET/CT in 20 patients, with 1 discordant finding in the lung.The combined F-NaF/F-FDG PET/CT scan allows for accurate evaluation of sarcoma patients. Further evaluation of this proposed imaging modality is warranted to identify the most suitable clinical scenarios, including initial treatment strategy and evaluation of response to therapy.

  View details for DOI 10.1097/RLU.0000000000000845

  View details for Web of Science ID 000359668600005

  View details for PubMedID 26053718

• Anaplastic Thyroid Carcinoma, Version 2.2015 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Haddad, R. I., Lydiatt, W. M., Ball, D. W., Busaidy, N. L., Byrd, D., Callender, G., Dickson, P., Duh, Q., Ehya, H., Haymart, M., Hoh, C., Hunt, J. P., Iagaru, A., Kandeel, F., Kopp, P., Lamonica, D. M., McCaffrey, J. C., Moley, J. F., Parks, L., Raeburn, C. D., Ridge, J. A., Ringel, M. D., Scheri, R. P., Shah, J. P., Smallridge, R. C., Sturgeon, C., Wang, T. N., Wirth, L. J., Hoffmann, K. G., Hughes, M. 2015; 13 (9): 1140-1150

  Abstract

  This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Thyroid Carcinoma focuses on anaplastic carcinoma because substantial changes were made to the systemic therapy recommendations for the 2015 update. Dosages and frequency of administration are now provided, docetaxel/doxorubicin regimens were added, and single-agent cisplatin was deleted because it is not recommended for patients with advanced or metastatic anaplastic thyroid cancer.

  View details for Web of Science ID 000361419800013

  View details for PubMedID 26358798

  View details for PubMedCentralID PMC4986600

• Fusion dual-tracer SPECT-based hepatic dosimetry predicts outcome after radioembolization for a wide range of tumour cell types EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Lam, M. G., Banerjee, A., Goris, M. L., Iagaru, A. H., Mittra, E. S., Louie, J. D., Sze, D. Y. 2015; 42 (8): 1192-1201

  Abstract

  Fusion dual-tracer SPECT imaging enables physiological rather than morphological voxel-based partitioning and dosimetry for (90)Y hepatic radioembolization (RE). We evaluated its prognostic value in a large heterogeneous cohort of patients with extensive hepatic malignancy.A total of 122 patients with primary or secondary liver malignancy (18 different cell types) underwent SPECT imaging after intraarterial injection of (99m)Tc macroaggregated albumin (TcMAA) as a simulation of subsequent (90)Y microsphere distribution, followed by administration of an excess of intravenous (99m)Tc-labelled sulphur colloid (TcSC) as a biomarker for functional liver, and a second SPECT scan. TcMAA distribution was used to estimate (90)Y radiation absorbed dose in tumour (D T) and in functional liver. Laboratory and clinical follow-up were recorded for 12 weeks after RE, and radiographic responses according to (m)RECIST were evaluated at 3 and 6 months. Dose-response relationships were determined for efficacy and toxicity.Patients were treated with a median of 1.73 GBq activity of resin microspheres (98 patients) or glass microspheres (24 patients), in a whole-liver approach (97 patients) or a lobar approach (25 patients). The objective response rate was 41 % at 3 months and 48 % at 6 months. Response was correlated with D T (P < 0.01). Median overall survival was 10.1 months (95 % confidence interval 7.4 - 12.8 months). Responders lived for 36.0 months compared to 8.7 months for nonresponders (P < 0.01). Stratified for tumour cell type, D T was independently associated with survival (P < 0.01). Absorbed dose in functional liver was correlated with toxicity grade change (P < 0.05) and RE-induced liver disease (P < 0.05).Fusion dual-tracer SPECT imaging offers a physiology-based functional imaging tool to predict efficacy and toxicity of RE. This technique can be refined to define dosing thresholds for specific tumour types and treatments, but appears generally predictive even in a heterogeneous cohort.

  View details for DOI 10.1007/s00259-015-3048-z

  View details for PubMedID 25916740

• Stereotactic ablative radiotherapy for the treatment of refractory cardiac ventricular arrhythmia. Circulation. Arrhythmia and electrophysiology Loo, B. W., Soltys, S. G., Wang, L., Lo, A., Fahimian, B. P., Iagaru, A., Norton, L., Shan, X., Gardner, E., Fogarty, T., Maguire, P., Al-Ahmad, A., Zei, P. 2015; 8 (3): 748-750

  View details for DOI 10.1161/CIRCEP.115.002765

  View details for PubMedID 26082532

• New Training Pathways to Dual Certification in Nuclear Medicine and Radiology JOURNAL OF NUCLEAR MEDICINE Harolds, J. A., Oates, M., Guiberteau, M. J., Ghesani, M., Scanlon, M. H., Iagaru, A. H. 2015; 56 (6): 17N–18N

  View details for PubMedID 26033625

• Ra-223 experience in pretreated patients: EAP setting. Sartor, A., Fernandez, D., Morris, M. J., Iagaru, A., Brown, A., Almeida, F., Sweeney, C., Smith, M., Dicker, A., Wong, Y., Shore, N. D., Gratt, J., Petrenciuc, O., Germino, J., Vogelzang, N. J. AMER SOC CLINICAL ONCOLOGY. 2015

  View details for Web of Science ID 000358036901108

• Glioblastoma Multiforme Recurrence: An Exploratory Study of (18)F FPPRGD2 PET/CT. Radiology Iagaru, A., Mosci, C., Mittra, E., Zaharchuk, G., Fischbein, N., Harsh, G., Li, G., Nagpal, S., Recht, L., Gambhir, S. S. 2015: 141550

  Abstract

  Purpose To prospectively evaluate fluorine 18 ((18)F) 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) (FPPRGD2) positron emission tomography (PET) in patients with glioblastoma multiforme (GBM). Materials and Methods The institutional review board approved this HIPAA-compliant protocol. Written informed consent was obtained from each patient. (18)F FPPRGD2 uptake was measured semiquantitatively in the form of maximum standardized uptake values (SUVmax) and uptake volumes before and after treatment with bevacizumab. Vital signs and laboratory results were collected before, during, and after the examinations. A nonparametric version of multivariate analysis of variance was used to assess safety outcome measures simultaneously across time points. A paired two-sample t test was performed to compare SUVmax. Results A total of 17 participants (eight men, nine women; age range, 25-65 years) were enrolled prospectively. (18)F FPPRGD2 PET/computed tomography (CT), (18)F fluorodeoxyglucose (FDG) PET/CT, and brain magnetic resonance (MR) imaging were performed within 3 weeks, prior to the start of bevacizumab therapy. In eight of the 17 patients (47%), (18)F FPPRGD2 PET/CT was repeated 1 week after the start of bevacizumab therapy; six patients (35%) underwent (18)F FPPRGD2 PET/CT a third time 6 weeks after starting bevacizumab therapy. There were no changes in vital signs, electrocardiographic findings, or laboratory values that qualified as adverse events. One patient (6%) had recurrent GBM identified only on (18)F FPPRGD2 PET images, and subsequent MR images enabled confirmation of recurrence. Of the 17 patients, 14 (82%) had recurrent GBM identified on (18)F FPPRGD2 PET and brain MR images, while (18)F FDG PET enabled identification of recurrence in 13 (76%) patients. Two patients (12%) had no recurrent GBM. Conclusion (18)F FPPRGD2 is a safe PET radiopharmaceutical that has increased uptake in GBM lesions. Larger cohorts are required to confirm these preliminary findings. (©) RSNA, 2015 Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.2015141550

  View details for PubMedID 25965900

• Semiquantitative Analysis of the Biodistribution of the Combined F-18-NaF and F-18-FDG Administration for PET/CT Imaging JOURNAL OF NUCLEAR MEDICINE Minamimoto, R., Mosci, C., Jamali, M., Barkhodari, A., Habte, F., Jackson, T., Mittra, E., Gambhir, S. S., Iagaru, A. 2015; 56 (5): 688-694

  Abstract

  In this study we evaluated the biodistribution of the (18)F-/(18)F-FDG administration compared to separate (18)F-NaF and (18)F-FDG. We also estimated the interaction of (18)F-NaF and (18)F-FDG in the (18)F-/(18)F-FDG administration by semiquantitative analysis.We retrospectively analyzed data of 49 patients (male 39, female 10; mean ± SD age: 59.3 ± 15.2 years) who had separate (18)F-FDG PET/CT and (18)F-NaF PET/CT, as well as the (18)F-/(18)F-FDG PET/CT sequentially. The most common primary diagnosis was prostate cancer (n = 28), followed by sarcoma (n = 9) and breast cancer (n = 6). The mean standardized uptake values (SUVmean) were recorded for 18 organs in all patients, while maximum SUV (SUVmax) and SUVmean were recorded for all the identified malignant lesions. We also estimated the (18)F-/(18)F-FDG uptake by sum of (18)F-FDG uptake and adjusted (18)F-NaF uptake based on the ratio of (18)F-NaF injected dose in (18)F-/(18)F-FDG PET/CT. Lastly, we compared the results in order to explore the interaction of (18)F-FDG and (18)F-NaF uptake in the (18)F-/(18)F-FDG scan.The (18)F-/(18)F-FDG uptake in the cerebral cortex, cerebellum, parotid grand, myocardium and bowel mostly reflect the (18)F-FDG uptake, while the uptake in the other analyzed structures is influenced by both the (18)F-FDG and the (18)F-NaF uptake. The (18)F-/(18)F-FDG uptake in extra skeletal lesions shows no significant difference when compared to the uptake from the separate (18)F-FDG scan. The (18)F-/(18)F-FDG uptake in skeletal lesions reflected mostly the (18)F-NaF uptake. Tumor to background (T/B) ratio of (18)F-/(18)F-FDG in extra skeletal lesions showed no significant difference when compared with that from (18)F-FDG alone (P = 0.73). For skeletal lesions, T/B ratio of (18)F-/(18)F-FDG was lower than that from (18)F-NaF alone (P <0.001); however, this difference did not result in missed skeletal lesions on the (18)F-/(18)F-FDG scan.The understanding of the biodistribution of radiopharmaceuticals and the lesions uptake of the (18)F-/(18)F-FDG scan, as well as the variations compared to the uptake on the separate (18)F-FDG PET/CT and (18)F-NaF PET/CT are valuable for more in depth evaluation of the combined scanning technique.

  View details for DOI 10.2967/jnumed.115.153767

  View details for Web of Science ID 000353831000013

  View details for PubMedID 25840978

• Physiological distribution of Ga-68-DOTA-TATE: an atlas of standardized uptake values Moradi, F., Minamimoto, R., Jamali, M., Barkhodari, A., Quon, A., Mittra, E., Gambhir, S., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2015

  View details for Web of Science ID 000358738802255

• F-18 FPPRGD(2) PET as a Surrogate Biomarker of Integrin alpha(v)beta(3) Expression Before and After Anti-angiogenesis Treatment 18 Minamimoto, R., Jamali, M., Barkhodari, A., Mosci, C., Mittra, E., Shen, B., Chin, F., Gambhir, S., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2015

  View details for Web of Science ID 000358738801280

• Prospective evaluation of Tc-99m MDP scintigraphy, F-18 NaF/F-18 FDG PET/CT and WBMRI in patients with breast and prostate cancers Iagaru, A., Minamimoto, R., Mosci, C., Jamali, M., Barkhodari, A., Loening, A., Taviani, V., Mittra, E., Gambhir, S., Vasanawala, S. SOC NUCLEAR MEDICINE INC. 2015

  View details for Web of Science ID 000358738802275

• Imaging patients with breast and prostate cancers using combined F-18 NaF/F-18 FDG and TOF simultaneous PET/MRI Iagaru, A., Minamimoto, R., Jamali, M., Barkhodari, A., Obara, P., Loening, A., Taviani, V., Mittra, E., Gambhir, S., Vasanawala, S. SOC NUCLEAR MEDICINE INC. 2015

  View details for Web of Science ID 000358738803075

• A convenient production of clinical grade Ga-68-labeled Bombesin in an automated cassette-based platform. Schneider, B., Zerna, M., Iagaru, A., Mueller, A., Berndt, M., Chin, F. SOC NUCLEAR MEDICINE INC. 2015

  View details for Web of Science ID 000358738801333

• Standard OSEM vs. Q.Clear (R) PET image reconstruction: an analysis of phantom data. Lantos, J., Iagaru, A., Levin, C. SOC NUCLEAR MEDICINE INC. 2015

  View details for Web of Science ID 000358738800264

• Ga-68-PRGD(2) and F-18-FDG PET/CT for differentiating uncommon meningioma with severe peritumoral edema mimicking glioma Li, D., Zhao, X., Ji, N., Xu, G., Mittra, E., Iagaru, A., Zhu, Z. SOC NUCLEAR MEDICINE INC. 2015

  View details for Web of Science ID 000358738801153

• Ga-68-DOTATATE uptake in patients with neuroendocrine tumors Moradi, F., Barkhodari, A., Jamali, M., Minamimoto, R., Schneider, B., Chin, F. T., Mittra, E. S., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2015

  View details for Web of Science ID 000353816700052

• PET/MR Oncologic Whole Body Workflow Optimization Holley, D., Zaharchuk, G., Vasanawala, S., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2015

  View details for Web of Science ID 000358738804072

• Ga-68 DOTA TATE PET/CT in patients with neuroendocrine tumors: a technologist's perspective Luan Nguyen, Moradi, F., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2015

  View details for Web of Science ID 000358738804051

• 18F-sodium fluoride PET/CT in oncology: an atlas of SUVs. Clinical nuclear medicine Sabbah, N., Jackson, T., Mosci, C., Jamali, M., Minamimoto, R., Quon, A., Mittra, E. S., Iagaru, A. 2015; 40 (4): e228-31

  Abstract

  The purpose of this study was to analyze the distribution of F Sodium Fluoride (F-NaF) uptake in the normal skeleton, benign and malignant bone lesions, and extraskeletal tissues, using semiquantitative SUV measurements.We retrospectively analyzed data from 129 patients who had F-NaF PET/CT at our institution for an oncological diagnosis between 2007 and 2014. There were 99 men and 30 women, 19 to 90 years old (mean [SD], 61.5 [15.5]). The range, average, and SD of SUV were measured for normal bone and extraskeletal tissues uptake for the entire patient population. A separate statistical analysis was performed to compare group A, which corresponds to the population of patient with no F-NaF-avid metastatic lesions, and group B, which corresponds to the population of patient with F-NaF-avid metastatic lesions. We also measured SUVmax and SUVmean for bony metastases and degenerative changesThe PET/CT images were acquired at 30 to 169 minutes (mean [SD], 76.5 [22.8]) after injection of 3.9 to 13.6 mCi (mean [SD], 7.3 [2.4]) of F-NaF. The range and mean (SD) of SUVmax for F-NaF-avid metastasis were 4.5 to 103.3 and 25.9 (16.6) and for F-NaF-avid degenerative changes were 3.3 to 52.1 and 16.5 (7.9), respectively.Various skeletal sites have different normal SUVs. Skeletal metastases have different SUVs when compared with benign findings such as degenerative changes.

  View details for DOI 10.1097/RLU.0000000000000633

  View details for PubMedID 25546225

• Dual-tracer imaging of malignant bone involvement using PET CLINICAL AND TRANSLATIONAL IMAGING Moradi, F., Iagaru, A. 2015; 3 (2): 123–31

  View details for DOI 10.1007/s40336-015-0106-2

  View details for Web of Science ID 000218682900005

• F-18-Sodium Fluoride PET/CT in Oncology An Atlas of SUVs CLINICAL NUCLEAR MEDICINE Sabbah, N., Jackson, T., Mosci, C., Jamali, M., Minamimoto, R., Quon, A., Mittra, E. S., Iagaru, A. 2015; 40 (4): E228-E231

  Abstract

  The purpose of this study was to analyze the distribution of F Sodium Fluoride (F-NaF) uptake in the normal skeleton, benign and malignant bone lesions, and extraskeletal tissues, using semiquantitative SUV measurements.We retrospectively analyzed data from 129 patients who had F-NaF PET/CT at our institution for an oncological diagnosis between 2007 and 2014. There were 99 men and 30 women, 19 to 90 years old (mean [SD], 61.5 [15.5]). The range, average, and SD of SUV were measured for normal bone and extraskeletal tissues uptake for the entire patient population. A separate statistical analysis was performed to compare group A, which corresponds to the population of patient with no F-NaF-avid metastatic lesions, and group B, which corresponds to the population of patient with F-NaF-avid metastatic lesions. We also measured SUVmax and SUVmean for bony metastases and degenerative changesThe PET/CT images were acquired at 30 to 169 minutes (mean [SD], 76.5 [22.8]) after injection of 3.9 to 13.6 mCi (mean [SD], 7.3 [2.4]) of F-NaF. The range and mean (SD) of SUVmax for F-NaF-avid metastasis were 4.5 to 103.3 and 25.9 (16.6) and for F-NaF-avid degenerative changes were 3.3 to 52.1 and 16.5 (7.9), respectively.Various skeletal sites have different normal SUVs. Skeletal metastases have different SUVs when compared with benign findings such as degenerative changes.

  View details for Web of Science ID 000352219100003

  View details for PubMedID 25546225

• Radioembolization Dosimetry: The Road Ahead CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY Smits, M. L., Elschot, M., Sze, D. Y., Kao, Y. H., Nijsen, J. F., Iagaru, A. H., de Jong, H. W., Van den Bosch, M. A., Lam, M. G. 2015; 38 (2): 261-269

  Abstract

  Methods for calculating the activity to be administered during yttrium-90 radioembolization (RE) are largely based on empirical toxicity and efficacy analyses, rather than dosimetry. At the same time, it is recognized that treatment planning based on proper dosimetry is of vital importance for the optimization of the results of RE. The heterogeneous and often clustered intrahepatic biodistribution of millions of point-source radioactive particles poses a challenge for dosimetry. Several studies found a relationship between absorbed doses and treatment outcome, with regard to both toxicity and efficacy. This should ultimately lead to improved patient selection and individualized treatment planning. New calculation methods and imaging techniques and a new generation of microspheres for image-guided RE will all contribute to these improvements. The aim of this review is to give insight into the latest and most important developments in RE dosimetry and to suggest future directions on patient selection, individualized treatment planning, and study designs.

  View details for DOI 10.1007/s00270-014-1042-7

  View details for Web of Science ID 000351155100002

  View details for PubMedID 25537310

• Detection of osseous metastasis by 18F-NaF/18F-FDG PET/CT versus CT alone. Clinical nuclear medicine Sampath, S. C., Sampath, S. C., Mosci, C., Lutz, A. M., Willmann, J. K., Mittra, E. S., Gambhir, S. S., Iagaru, A. 2015; 40 (3): e173-7

  Abstract

  Sodium fluoride PET (F-NaF) has recently reemerged as a valuable method for detection of osseous metastasis, with recent work highlighting the potential of coadministered F-NaF and F-FDG PET/CT in a single combined imaging examination. We further examined the potential of such combined examinations by comparing dual tracer F-NaF/F-FDG PET/CT with CT alone for detection of osseous metastasis.Seventy-five participants with biopsy-proven malignancy were consecutively enrolled from a single center and underwent combined F-NaF/F-FDG PET/CT and diagnostic CT scans. PET/CT as well as CT only images were reviewed in blinded fashion and compared with the results of clinical, imaging, or histological follow-up as a truth standard.Sensitivity of the combined F-NaF/F-FDG PET/CT was higher than that of CT alone (97.4% vs 66.7%). CT and F-NaF/F-FDG PET/CT were concordant in 73% of studies. Of 20 discordant cases, F-NaF/F-FDG PET/CT was correct in 19 (95%). Three cases were interpreted concordantly but incorrectly, and all 3 were false positives. A single case of osseous metastasis was detected by CT alone, but not by F-NaF/F-FDG PET/CT.Combined F-NaF/F-FDG PET/CT outperforms CT alone and is highly sensitive and specific for detection of osseous metastases. The concordantly interpreted false-positive cases demonstrate the difficulty of distinguishing degenerative from malignant disease, whereas the single case of metastasis seen on CT but not PET highlights the need for careful review of CT images in multimodality studies.

  View details for DOI 10.1097/RLU.0000000000000560

  View details for PubMedID 25140557

• Prior and concurrent use of abiraterone and enzalutamide with Ra-223 in an expanded access setting. Sartor, A., Fernandez, D., Morris, M. J., Iagaru, A., Brown, A., Almeida, F., Sweeney, C., Smith, M., Dicker, A., Wong, Y., Shore, N. D., Gratt, J., Petrenciuc, O., Vogelzang, N. J. AMER SOC CLINICAL ONCOLOGY. 2015

  View details for DOI 10.1200/jco.2015.33.7_suppl.253

  View details for Web of Science ID 000356886700254

• Radium-223 dichloride (Ra-223) in US expanded access program (EAP). Vogelzang, N. J., Fernandez, D., Morris, M. J., Iagaru, A., Brown, A., Almeida, F., Sweeney, C., Smith, M., Dicker, A., Wong, Y., Shore, N. D., Bangerter, K., Petrenciuc, O., Sartor, A. AMER SOC CLINICAL ONCOLOGY. 2015

  View details for DOI 10.1200/jco.2015.33.7_suppl.247

  View details for Web of Science ID 000356886700248

• Detection of Osseous Metastasis by 18F-NaF/18F-FDG PET/CT Versus CT Alone. Clinical nuclear medicine Sampath, S. C., Sampath, S. C., Mosci, C., Lutz, A. M., Willmann, J. K., Mittra, E. S., Gambhir, S. S., Iagaru, A. 2015; 40 (3): e173-7

  Abstract

  Sodium fluoride PET (F-NaF) has recently reemerged as a valuable method for detection of osseous metastasis, with recent work highlighting the potential of coadministered F-NaF and F-FDG PET/CT in a single combined imaging examination. We further examined the potential of such combined examinations by comparing dual tracer F-NaF/F-FDG PET/CT with CT alone for detection of osseous metastasis.Seventy-five participants with biopsy-proven malignancy were consecutively enrolled from a single center and underwent combined F-NaF/F-FDG PET/CT and diagnostic CT scans. PET/CT as well as CT only images were reviewed in blinded fashion and compared with the results of clinical, imaging, or histological follow-up as a truth standard.Sensitivity of the combined F-NaF/F-FDG PET/CT was higher than that of CT alone (97.4% vs 66.7%). CT and F-NaF/F-FDG PET/CT were concordant in 73% of studies. Of 20 discordant cases, F-NaF/F-FDG PET/CT was correct in 19 (95%). Three cases were interpreted concordantly but incorrectly, and all 3 were false positives. A single case of osseous metastasis was detected by CT alone, but not by F-NaF/F-FDG PET/CT.Combined F-NaF/F-FDG PET/CT outperforms CT alone and is highly sensitive and specific for detection of osseous metastases. The concordantly interpreted false-positive cases demonstrate the difficulty of distinguishing degenerative from malignant disease, whereas the single case of metastasis seen on CT but not PET highlights the need for careful review of CT images in multimodality studies.

  View details for DOI 10.1097/RLU.0000000000000560

  View details for PubMedID 25140557

• 123I accumulation in thoracic neoesophagus masking residual papillary thyroid cancer. Clinical nuclear medicine Jackson, T., Sabbah, N., Iagaru, A. 2015; 40 (2): e150-1

  Abstract

  A 56-year-old woman with prior esophageal resection and reconstruction after accidental lye ingestion presented for management of recently diagnosed thyroid cancer. She had total thyroidectomy with pathology demonstrating bilateral well-differentiated papillary thyroid cancer measuring up to 1.0 cm and positive margins. Approximately 1 month after surgery, I whole-body scan was obtained. Planar images demonstrated linear I uptake in the thorax, compatible with accumulation in the neoesophagus. Given the patient's postsurgical anatomy, SPECT/CT of the thorax was done and demonstrated additional focal I uptake in the left lower neck, compatible with residual thyroid tissue versus thyroid cancer (lymph node metastasis).

  View details for DOI 10.1097/RLU.0000000000000499

  View details for PubMedID 24999691

• Simultaneous Whole-Body Time-of-Flight F-18-FDG PET/MRI A Pilot Study Comparing SUVmax With PET/CT and Assessment of MR Image Quality CLINICAL NUCLEAR MEDICINE Iagaru, A., Mittra, E., Minamimoto, R., Jamali, M., Levin, C., Quon, A., Gold, G., Herfkens, R., Vasanawala, S., Gambhir, S. S., Zaharchuk, G. 2015; 14 (1): 1-8

  Abstract

  The recent introduction of hybrid PET/MRI scanners in clinical practice has shown promising initial results for several clinical scenarios. However, the first generation of combined PET/MRI lacks time-of-flight (TOF) technology. Here we report the results of the first patients to be scanned on a completely novel fully integrated PET/MRI scanner with TOF.We analyzed data from patients who underwent a clinically indicated F FDG PET/CT, followed by PET/MRI. Maximum standardized uptake values (SUVmax) were measured from F FDG PET/MRI and F FDG PET/CT for lesions, cerebellum, salivary glands, lungs, aortic arch, liver, spleen, skeletal muscle, and fat. Two experienced radiologists independently reviewed the MR data for image quality.Thirty-six patients (19 men, 17 women, mean [±standard deviation] age of 61 ± 14 years [range: 27-86 years]) with a total of 69 discrete lesions met the inclusion criteria. PET/CT images were acquired at a mean (±standard deviation) of 74 ± 14 minutes (range: 49-100 minutes) after injection of 10 ± 1 mCi (range: 8-12 mCi) of F FDG. PET/MRI scans started at 161 ± 29 minutes (range: 117 - 286 minutes) after the F FDG injection. All lesions identified on PET from PET/CT were also seen on PET from PET/MRI. The mean SUVmax values were higher from PET/MRI than PET/CT for all lesions. No degradation of MR image quality was observed.The data obtained so far using this investigational PET/MR system have shown that the TOF PET system is capable of excellent performance during simultaneous PET/MR with routine pulse sequences. MR imaging was not compromised. Comparison of the PET images from PET/CT and PET/MRI show no loss of image quality for the latter. These results support further investigation of this novel fully integrated TOF PET/MRI instrument.

  View details for Web of Science ID 000346633400023

• Does The White Blood Cell Count Assist With Solitary Pulmonary Nodule Diagnosis? Nair, V. S., Rosenberg, J., Horng, G., Jamali, M., Tripathi, P., Iagaru, A., Kuschner, W., Vasanawala, M., Gambhir, S. S., Thoracic Oncology AMER THORACIC SOC. 2015

  View details for Web of Science ID 000377582804215

• Scanner Dependent Noise Properties of the Q.Clear PET Image Reconstruction Tool Lantos, J., Iagaru, A., Levin, C. S., IEEE IEEE. 2015

  View details for Web of Science ID 000413680600458

• Validation of 64Cu-DOTA-rituximab injection preparation under good manufacturing practices: a PET tracer for imaging of B-cell non-Hodgkin lymphoma. Molecular imaging Natarajan, A., Arksey, N., Iagaru, A., Chin, F. T., Gambhir, S. S. 2015; 14

  View details for DOI 10.2310/7290.2014.00055

  View details for PubMedID 25762106

• Validation of 64Cu-DOTA-rituximab injection preparation under good manufacturing practices: a PET tracer for imaging of B-cell non-Hodgkin lymphoma. Molecular imaging Natarajan, A., Arksey, N., Iagaru, A., Chin, F. T., Gambhir, S. S. 2015; 14

  Abstract

  AbstractManufacturing of 64Cu-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-rituximab injection under good manufacturing practices (GMP) was validated for imaging of patients with CD20+ B-cell non-Hodgkin lymphoma. Rituximab was purified by size exclusion high performance liquid chromatography (HPLC) and conjugated to DOTA-mono-(N-hydroxysuccinimidyl) ester. 64CuCl2, buffers, reagents, and other raw materials were obtained as high-grade quality. Following a semi-automated synthesis of 64Cu-DOTA-rituximab, a series of quality control tests was performed. The product was further tested in vivo using micro-positron emission tomography/computed tomography (PET/CT) to assess targeting ability towards human CD20 in transgenic mice. Three batches of 64Cu-DOTA-rituximab final product were prepared as per GMP specifications. The radiolabeling yield from these batches was 93.1 ± 5.8%; these provided final product with radiopharmaceutical yield, purity, and specific activity of 59.2 ± 5.1% (0.9 ± 0.1 GBq of 64Cu), > 95% (by HPLC and radio-thin layer chromatography), and 229.4 ± 43.3 GBq/µmol (or 1.5 ± 0.3 MBq/µg), respectively. The doses passed apyrogenicity and human serum stability specifications, were sterile up to 14 days, and retained > 60% immunoreactivity. In vivo micro-PET/CT mouse images at 24 hours postinjection showed that the tracer targeted the intended sites of human CD20 expression. Thus, we have validated the manufacturing of GMP grade 64Cu-DOTA-rituximab for injection in the clinical setting.

  View details for DOI 10.2310/7290.2014.00055

  View details for PubMedID 25762106

• Simultaneous whole-body time-of-flight 18F-FDG PET/MRI: a pilot study comparing SUVmax with PET/CT and assessment of MR image quality. Clinical nuclear medicine Iagaru, A., Mittra, E., Minamimoto, R., Jamali, M., Levin, C., Quon, A., Gold, G., Herfkens, R., Vasanawala, S., Gambhir, S. S., Zaharchuk, G. 2015; 40 (1): 1-8

  Abstract

  The recent introduction of hybrid PET/MRI scanners in clinical practice has shown promising initial results for several clinical scenarios. However, the first generation of combined PET/MRI lacks time-of-flight (TOF) technology. Here we report the results of the first patients to be scanned on a completely novel fully integrated PET/MRI scanner with TOF.We analyzed data from patients who underwent a clinically indicated F FDG PET/CT, followed by PET/MRI. Maximum standardized uptake values (SUVmax) were measured from F FDG PET/MRI and F FDG PET/CT for lesions, cerebellum, salivary glands, lungs, aortic arch, liver, spleen, skeletal muscle, and fat. Two experienced radiologists independently reviewed the MR data for image quality.Thirty-six patients (19 men, 17 women, mean [±standard deviation] age of 61 ± 14 years [range: 27-86 years]) with a total of 69 discrete lesions met the inclusion criteria. PET/CT images were acquired at a mean (±standard deviation) of 74 ± 14 minutes (range: 49-100 minutes) after injection of 10 ± 1 mCi (range: 8-12 mCi) of F FDG. PET/MRI scans started at 161 ± 29 minutes (range: 117 - 286 minutes) after the F FDG injection. All lesions identified on PET from PET/CT were also seen on PET from PET/MRI. The mean SUVmax values were higher from PET/MRI than PET/CT for all lesions. No degradation of MR image quality was observed.The data obtained so far using this investigational PET/MR system have shown that the TOF PET system is capable of excellent performance during simultaneous PET/MR with routine pulse sequences. MR imaging was not compromised. Comparison of the PET images from PET/CT and PET/MRI show no loss of image quality for the latter. These results support further investigation of this novel fully integrated TOF PET/MRI instrument.

  View details for DOI 10.1097/RLU.0000000000000611

  View details for PubMedID 25489952

• Thyroid Carcinoma, Version 2.2014 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Tuttle, R. M., Haddad, R. I., Ball, D. W., Byrd, D., Dickson, P., Duh, Q., Ehya, H., Haymart, M., Hoh, C., Hunt, J. P., Iagaru, A., Kandeel, F., Kopp, P., Lamonica, D. M., Lydiatt, W. M., McCaffrey, J., Moley, J. F., Parks, L., Raeburn, C. D., Ridge, J. A., Ringel, M. D., Scheri, R. P., Shah, J. P., Sherman, S. I., Sturgeon, C., Waguespack, S. G., Wang, T. N., Wirth, L. J., Hoffmann, K. G., Hughes, M. 2014; 12 (12): 1671-1680

  Abstract

  These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on "Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer" was added to the NCCN Guidelines to assist with using these novel targeted agents.

  View details for Web of Science ID 000346190900005

• Thyroid carcinoma, version 2.2014. Journal of the National Comprehensive Cancer Network Tuttle, R. M., Haddad, R. I., Ball, D. W., Byrd, D., Dickson, P., Duh, Q., Ehya, H., Haymart, M., Hoh, C., Hunt, J. P., Iagaru, A., Kandeel, F., Kopp, P., Lamonica, D. M., Lydiatt, W. M., McCaffrey, J., Moley, J. F., Parks, L., Raeburn, C. D., Ridge, J. A., Ringel, M. D., Scheri, R. P., Shah, J. P., Sherman, S. I., Sturgeon, C., Waguespack, S. G., Wang, T. N., Wirth, L. J., Hoffmann, K. G., Hughes, M. 2014; 12 (12): 1671-1680

  Abstract

  These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on "Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer" was added to the NCCN Guidelines to assist with using these novel targeted agents.

  View details for PubMedID 25505208

• (18)F-FPPRGD2 PET/CT: pilot phase evaluation of breast cancer patients. Radiology Iagaru, A., Mosci, C., Shen, B., Chin, F. T., Mittra, E., Telli, M. L., Gambhir, S. S. 2014; 273 (2): 549-559

  Abstract

  Purpose To present data from the first prospective pilot phase trial of breast cancer participants imaged with fluorine 18 ((18)F)-2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) (FPPRGD2), a radiopharmaceutical agent used in positron emission tomographic (PET) imaging. Materials and Methods The local institutional review board approved the HIPAA-compliant protocol. Written informed consent was obtained from each patient. Eight women (age range, 44-67 years; mean age, 54.3 years ± 8.8 [standard deviation]) with newly diagnosed or recurrent breast cancer were recruited between November 2010 and February 2011. (18)F-FPPRGD2 PET/computed tomographic (CT) and (18)F-fluorodeoxyglucose (FDG) PET/CT examinations were performed within 3 weeks of each other. Dynamic (18)F-FPPRGD2 PET and two whole-body static (18)F-FPPRGD2 PET/CT scans were obtained. During this time, vital signs and electrocardiograms were recorded at regular intervals. Blood samples were obtained before the injection of (18)F-FPPRGD2 and at 24 hours and 1 week after injection to evaluate for toxicity. A nonparametric version of multivariate analysis of variance was used to assess the safety outcome measures simultaneously across time points. A paired two-sample t test was performed to compare the maximum standardized uptake values (SUVmax). Results (18)F-FPPRGD2 was well tolerated, without noticeable changes in vital signs, on electrocardiograms, or in laboratory values. A total of 30 lesions were evaluated at (18)F-FDG PET/CT and (18)F-FPPRGD2 PET/CT. The primary breast lesions had (18)F-FPPRGD2 uptake with SUVmax of 2.4-9.4 (mean, 5.6 ± 2.8) 60 minutes after injection, compared with (18)F-FDG uptake with SUVmax of 2.8-18.6 (mean, 10.4 ± 7.2). Metastatic lesions also showed (18)F-FPPRGD2 uptake, with SUVmax of 2.4-9.7 (mean, 5.0 ± 2.3) at 60 minutes, compared with (18)F-FDG uptake with SUVmax of 2.2-14.6 (mean, 6.6 ± 4.2). Conclusion Data from this pilot phase study suggest that (18)F-FPPRGD2 is a safe PET radiopharmaceutical agent. Evaluation of (18)F-FPPRGD2 in participants with breast cancer demonstrated significant uptake in the primary lesion and in the metastases. Larger cohorts are required to confirm these preliminary findings. © RSNA, 2014.

  View details for DOI 10.1148/radiol.14140028

  View details for PubMedID 25033190

• Successful treatment of systemic and central nervous system post-transplant lymphoproliferative disorder without the use of high-dose methotrexate or radiation. Pediatric blood & cancer Mahapatra, S., Chin, C. C., Iagaru, A., Heerema-McKenney, A., Twist, C. J. 2014; 61 (11): 2107-2109

  Abstract

  Post-transplant lymphoproliferative disorder (PTLD) describes a spectrum of conditions with highest incidence in the first year post-solid organ transplant in pediatric patients. Central nervous system (CNS) involvement with PTLD carries high mortality risk with no consensus on optimal therapeutic regimen. We present the case of a 7-year old heart transplant patient diagnosed with widespread monomorphic, CD20+, Epstein-Barr virus-positive PTLD, including CNS involvement. In addition to immunosuppression reduction and rituximab, she was treated with multiagent systemic and intrathecal chemotherapy. She achieved a prompt and complete clinical and radiologic remission, which has been sustained for over 46 months since diagnosis.

  View details for DOI 10.1002/pbc.25129

  View details for PubMedID 25066638

• Successful Treatment of Systemic and Central Nervous System Post-Transplant Lymphoproliferative Disorder Without the Use of High-Dose Methotrexate or Radiation PEDIATRIC BLOOD & CANCER Mahapatra, S., Chin, C. C., Iagaru, A., Heerema-McKenney, A., Twist, C. J. 2014; 61 (11): 2107-2109

  Abstract

  Post-transplant lymphoproliferative disorder (PTLD) describes a spectrum of conditions with highest incidence in the first year post-solid organ transplant in pediatric patients. Central nervous system (CNS) involvement with PTLD carries high mortality risk with no consensus on optimal therapeutic regimen. We present the case of a 7-year old heart transplant patient diagnosed with widespread monomorphic, CD20+, Epstein-Barr virus-positive PTLD, including CNS involvement. In addition to immunosuppression reduction and rituximab, she was treated with multiagent systemic and intrathecal chemotherapy. She achieved a prompt and complete clinical and radiologic remission, which has been sustained for over 46 months since diagnosis.

  View details for DOI 10.1002/pbc.25129

  View details for Web of Science ID 000342723300041

• F-18 NaF Brain Metastasis Uptake in a Patient with Melanoma CLINICAL NUCLEAR MEDICINE Jones, R. P., Iagaru, A. 2014; 39 (10): E448–E450

  Abstract

  A 57-year-old man with a history of metastatic melanoma and sclerotic bone lesions seen on CT was referred for F NaF PET/CT evaluation of active skeletal metastases. While the bone lesions had no uptake and were therefore thought to represent sequela of previously treated disease, an unexpected area of F NaF uptake was identified in the left temporal lobe. Concurrent contrast-enhanced brain MRI re-demonstrated a large metastasis, also seen on previous MRI scans done at another institution.

  View details for PubMedID 24566410

• First evaluation of a time-of-flight whole-body PET/MRI scanner in oncology patients: comparison with PET/CT Iagaru, A., Jamali, M., Minamimoto, R., Mittra, E., Gold, G., Vasanwala, S., Gambhir, S. S., Zaharchuk, G. SPRINGER. 2014: S287–S288

  View details for Web of Science ID 000348841900416

• Improved automated clinical production of Ga-68-DOTA-TATE for targeting somatostatic receptor-positive neuroendocrine tumors Arksey, N., Schneider, B., Iagaru, A., Chin, F. T. AMER CHEMICAL SOC. 2014

  View details for Web of Science ID 000349167402040

• Circulating Tumor Microemboli Diagnostics for Patients with Non-Small-Cell Lung Cancer JOURNAL OF THORACIC ONCOLOGY Carlsson, A., Nair, V. S., Luttgen, M. S., Keu, K. V., Horng, G., Vasanawala, M., Kolatkar, A., Jamali, M., Iagaru, A. H., Kuschner, W., Loo, B. W., Shrager, J. B., Bethel, K., Hoh, C. K., Bazhenova, L., Nieva, J., Kuhn, P., Gambhir, S. S. 2014; 9 (8): 1111-1119

  Abstract

  Circulating tumor microemboli (CTM) are potentially important cancer biomarkers, but using them for cancer detection in early-stage disease has been assay limited. We examined CTM test performance using a sensitive detection platform to identify stage I non-small-cell lung cancer (NSCLC) patients undergoing imaging evaluation.First, we prospectively enrolled patients during 18F-FDG PET-CT imaging evaluation for lung cancer that underwent routine phlebotomy where CTM and circulating tumor cells (CTCs) were identified in blood using nuclear (DAPI), cytokeratin (CK), and CD45 immune-fluorescent antibodies followed by morphologic identification. Second, CTM and CTC data were integrated with patient (age, gender, smoking, and cancer history) and imaging (tumor diameter, location in lung, and maximum standard uptake value [SUVmax]) data to develop and test multiple logistic regression models using a case-control design in a training and test cohort followed by cross-validation in the entire group.We examined 104 patients with NSCLC, and the subgroup of 80 with stage I disease, and compared them to 25 patients with benign disease. Clinical and imaging data alone were moderately discriminating for all comers (Area under the Curve [AUC] = 0.77) and by stage I disease only (AUC = 0.77). However, the presence of CTM combined with clinical and imaging data was significantly discriminating for diagnostic accuracy in all NSCLC patients (AUC = 0.88, p value = 0.001) and for stage I patients alone (AUC = 0.87, p value = 0.002).CTM may add utility for lung cancer diagnosis during imaging evaluation using a sensitive detection platform.

  View details for PubMedID 25157764

• Performance of a high sensitivity time-of-flight PET ring operating simultaneously within a 3T MR system. EJNMMI physics Levin, C. S., Jansen, F., Deller, T., Maramraju, S. H., Grant, A., Iagaru, A. 2014; 1: A72-?

  View details for DOI 10.1186/2197-7364-1-S1-A72

  View details for PubMedID 26501663

  View details for PubMedCentralID PMC4545961

• Initial experience with 223Ra vial delivery (Alpharadin (R)) vs. unit dose delivery (Xofigo (R)) Castaneda, P., Leonard, Z., Wen, M., Kwofie, J., Mittra, E., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2014

  View details for Web of Science ID 000361438103361

• Combined NaF/FDG PET/CT evaluation of prostate cancer patients Iagaru, A., Mosci, C., Keu, K., Mittra, E., Hancock, S., Pachynski, R., Srinivas, S., Gambhir, S. SOC NUCLEAR MEDICINE INC. 2014

  View details for Web of Science ID 000361438102320

• FDG uptake in normal tissues and malignant lesions from the first whole-body time-of-flight PET/MRI scanner: Comparison with PET/CT Iagaru, A., Mittra, E., Zaharchuk, G., Frost, R., Elekes, A., Anderson, J., Bobb, C., Lahrman, J., Gold, G., Gambhir, S. SOC NUCLEAR MEDICINE INC. 2014

  View details for Web of Science ID 000361438101156

• Prospective evaluation of combined NaF/FDG PET/CT and whole-body MRI in patients with breast and prostate cancer Iagaru, A., Mosci, C., Jamali, M., Loening, A., Mittra, E., Gambhir, S., Vasanawala, S. SOC NUCLEAR MEDICINE INC. 2014

  View details for Web of Science ID 000361438102203

• Initial experience with 223Ra vial delivery (Alpharadin (R)) vs. unit dose delivery (Xofigo (R)) Castaneda, P., Leonard, Z., Wen, M., Kwofie, J., Mittra, E., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2014

  View details for Web of Science ID 000361438104351

• 18F-FDG PET/CT in the management of patients with post-transplant lymphoproliferative disorder. Nuclear medicine communications Takehana, C. S., Twist, C. J., Mosci, C., Quon, A., Mittra, E., Iagaru, A. 2014; 35 (3): 276-281

  Abstract

  Post-transplant lymphoproliferative disorder (PTLD) is a rare but serious complication in transplant patients. Although fluorine-18 2-fluoro-2-deoxyglucose PET and computed tomography (F-FDG PET/CT) has been used for the evaluation and management of patients with PTLD, its utility has yet to be documented. We were therefore prompted to review our experience with F-FDG PET/CT in PTLD.We retrospectively reviewed the records of consecutive patients who had undergone F-FDG PET/CT for evaluation of PTLD from January 2004 to June 2012 at our institution. F-FDG PET/CT scans were compared with other imaging modalities performed concurrently. A chart review of pertinent clinical information was also conducted.A total of 30 patients were identified (14 female and 16 male; 1.7-76.7 years of age, average: 23.8 years). Twenty-seven participants had biopsy-proven PTLD and another three had been treated for PTLD because of high clinical suspicion of disease and positive F-FDG PET/CT findings in the absence of histological diagnosis. Eighty-three percent of these PTLD patients had extranodal involvement. In 57% of the cases, F-FDG PET/CT detected occult lesions not identified on other imaging modalities or suggested PTLD in equivocal lesions. The more aggressive PTLD histological subtypes demonstrated higher SUVmax compared with the less aggressive subtypes.F-FDG PET/CT is beneficial in the diagnostic evaluation of patients with PTLD. F-FDG PET/CT has the ability to detect occult lesions not identified on other imaging modalities, particularly extranodal lesions. In addition, F-FDG PET/CT may predict the PTLD subtype, as the lesions with higher pathologic grade presented with significantly higher SUVmax compared with the less aggressive forms.

  View details for DOI 10.1097/MNM.0000000000000050

  View details for PubMedID 24296883

• The Clinical Use of PET/CT in the Evaluation of Melanoma. Methods in molecular biology (Clifton, N.J.) Keu, K. V., Iagaru, A. H. 2014; 1102: 553-580

  Abstract

  Positron emission tomography combined with computed tomography (PET/CT) has emerged in the last decade as a dominant imaging modality used for staging, monitoring response and surveillance of various cancers, including melanoma. Using 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) as the radiopharmaceutical, PET/CT has demonstrated its efficacy and its utility in the management of patients with advanced melanoma. Nonetheless, challenges remain in the early stage evaluation of melanoma and in the development of novel radiotracers to better characterize lesions found on PET/CT. This chapter focuses on the advantages and limitations of this imaging modality in melanoma. We also detail and describe the approach to perform (18)F-FDG PET/CT, the methods to accurately quantify lesions, as well as the pearls/pitfalls of image interpretation. Finally, an overview of preclinical and investigational clinical radiopharmaceuticals is presented.

  View details for DOI 10.1007/978-1-62703-727-3_30

  View details for PubMedID 24258999

• Root cause analysis of gastroduodenal ulceration after yttrium-90 radioembolization. Cardiovascular and interventional radiology Lam, M. G., Banerjee, S., Louie, J. D., Abdelmaksoud, M. H., Iagaru, A. H., Ennen, R. E., Sze, D. Y. 2013; 36 (6): 1536-1547

  Abstract

  INTRODUCTION: A root cause analysis was performed on the occurrence of gastroduodenal ulceration after hepatic radioembolization (RE). We aimed to identify the risk factors in the treated population and to determine the specific mechanism of nontarget RE in individual cases. METHODS: The records of 247 consecutive patients treated with yttrium-90 RE for primary (n = 90) or metastatic (n = 157) liver cancer using either resin (n = 181) or glass (n = 66) microspheres were reviewed. All patients who developed a biopsy-proven microsphere-induced gastroduodenal ulcer were identified. Univariate and multivariate analyses were performed on baseline parameters and procedural data to determine possible risk factors in the total population. Individual cases were analyzed to ascertain the specific cause, including identification of the culprit vessel(s) leading to extrahepatic deposition of the microspheres. RESULTS: Eight patients (3.2 %) developed a gastroduodenal ulcer. Stasis during injection was the strongest independent risk factor (p = 0.004), followed by distal origin of the gastroduodenal artery (p = 0.004), young age (p = 0.040), and proximal injection of the microspheres (p = 0.043). Prolonged administrations, pain during administration, whole liver treatment, and use of resin microspheres also showed interrelated trends in multivariate analysis. Retrospective review of intraprocedural and postprocedural imaging showed a probable or possible culprit vessel, each a tiny complex collateral vessel, in seven patients. CONCLUSION: Proximal administrations and those resulting in stasis of flow presented increased risk for gastroduodenal ulceration. Patients who had undergone bevacizumab therapy were at high risk for developing stasis.

  View details for DOI 10.1007/s00270-013-0579-1

  View details for PubMedID 23435742

• Prognostic Utility of Y-90 Radioembolization Dosimetry Based on Fusion Tc-99m-Macroaggregated Albumin-Tc-99m-Sulfur Colloid SPECT JOURNAL OF NUCLEAR MEDICINE Lam, M. G., Goris, M. L., Iagaru, A. H., Mittra, E. S., Louie, J. D., Sze, D. Y. 2013; 54 (12): 2055-2061

  Abstract

  Planning hepatic (90)Y radioembolization activity requires balancing toxicity with efficacy. We developed a dual-tracer SPECT fusion imaging protocol that merges data on radioactivity distribution with physiologic liver mapping.Twenty-five patients with colorectal carcinoma and bilobar liver metastases received whole-liver radioembolization with resin microspheres prescribed as per convention (mean administered activity, 1.69 GBq). As part of standard treatment planning, all patients underwent SPECT imaging after intraarterial injection of 37 MBq of (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) to simulate subsequent (90)Y distribution. Immediately afterward, patients received 185 MBq of labeled sulfur colloid ((99m)Tc-SC) intravenously as a biomarker for normal hepatic reticuloendothelial function and SPECT was repeated. The SPECT images were coregistered and fused. A region-based method was used to predict the (90)Y radiation absorbed dose to functional liver tissue (DFL) by calculation of (99m)Tc-MAA activity in regions with (99m)Tc-SC uptake. Similarly, the absorbed dose to tumor (DT) was predicted by calculation of (99m)Tc-MAA activity in voxels without (99m)Tc-SC uptake. Laboratory data and radiographic response were measured for 3 mo, and the survival of patients was recorded. SPECT-based DT and DFL were correlated with parameters of toxicity and efficacy.Toxicity, as measured by increase in serum liver enzymes, correlated significantly with SPECT-based calculation of DFL at all time points (P < 0.05) (mean DFL, 27.9 Gy). Broad biochemical toxicity (>50% increase in all liver enzymes) occurred at a DFL of 24.5 Gy and above. In addition, in uni- and multivariate analysis, SPECT-based calculation of DT (mean DT, 44.2 Gy) correlated with radiographic response (P < 0.001), decrease in serum carcinoembryonic antigen (P < 0.05), and overall survival (P < 0.01). The cutoff value of DT for prediction of 1-y survival was 55 Gy (area under the receiver-operating-characteristic curve = 0.86; P < 0.01). Patients who received a DT of more than 55 Gy had a median survival of 32.8 mo, compared with 7.2 mo in patients who received less (P < 0.05).Dual-tracer (99m)Tc-MAA-(99m)Tc-SC fusion SPECT offers a physiology-based imaging tool with significant prognostic power that may lead to improved personalized activity planning.

  View details for DOI 10.2967/jnumed.113.123257

  View details for Web of Science ID 000328013000006

• Combined 18F-fluoride and 18F-FDG PET/CT: a response based on actual data from prospective studies. European journal of nuclear medicine and molecular imaging Iagaru, A., Mosci, C., Dick, D. W., Sathekge, M., Lapa, P., de Lima, J. M., Gambhir, S. S. 2013; 40 (12): 1922-1924

  View details for DOI 10.1007/s00259-013-2556-y

  View details for PubMedID 24057457

• Prognostic utility of 90Y radioembolization dosimetry based on fusion 99mTc-macroaggregated albumin-99mTc-sulfur colloid SPECT. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Lam, M. G., Goris, M. L., Iagaru, A. H., Mittra, E. S., Louie, J. D., Sze, D. Y. 2013; 54 (12): 2055-2061

  Abstract

  Planning hepatic (90)Y radioembolization activity requires balancing toxicity with efficacy. We developed a dual-tracer SPECT fusion imaging protocol that merges data on radioactivity distribution with physiologic liver mapping.Twenty-five patients with colorectal carcinoma and bilobar liver metastases received whole-liver radioembolization with resin microspheres prescribed as per convention (mean administered activity, 1.69 GBq). As part of standard treatment planning, all patients underwent SPECT imaging after intraarterial injection of 37 MBq of (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) to simulate subsequent (90)Y distribution. Immediately afterward, patients received 185 MBq of labeled sulfur colloid ((99m)Tc-SC) intravenously as a biomarker for normal hepatic reticuloendothelial function and SPECT was repeated. The SPECT images were coregistered and fused. A region-based method was used to predict the (90)Y radiation absorbed dose to functional liver tissue (DFL) by calculation of (99m)Tc-MAA activity in regions with (99m)Tc-SC uptake. Similarly, the absorbed dose to tumor (DT) was predicted by calculation of (99m)Tc-MAA activity in voxels without (99m)Tc-SC uptake. Laboratory data and radiographic response were measured for 3 mo, and the survival of patients was recorded. SPECT-based DT and DFL were correlated with parameters of toxicity and efficacy.Toxicity, as measured by increase in serum liver enzymes, correlated significantly with SPECT-based calculation of DFL at all time points (P < 0.05) (mean DFL, 27.9 Gy). Broad biochemical toxicity (>50% increase in all liver enzymes) occurred at a DFL of 24.5 Gy and above. In addition, in uni- and multivariate analysis, SPECT-based calculation of DT (mean DT, 44.2 Gy) correlated with radiographic response (P < 0.001), decrease in serum carcinoembryonic antigen (P < 0.05), and overall survival (P < 0.01). The cutoff value of DT for prediction of 1-y survival was 55 Gy (area under the receiver-operating-characteristic curve = 0.86; P < 0.01). Patients who received a DT of more than 55 Gy had a median survival of 32.8 mo, compared with 7.2 mo in patients who received less (P < 0.05).Dual-tracer (99m)Tc-MAA-(99m)Tc-SC fusion SPECT offers a physiology-based imaging tool with significant prognostic power that may lead to improved personalized activity planning.

  View details for DOI 10.2967/jnumed.113.123257

  View details for PubMedID 24144563

• Safety of repeated yttrium-90 radioembolization. Cardiovascular and interventional radiology Lam, M. G., Louie, J. D., Iagaru, A. H., Goris, M. L., Sze, D. Y. 2013; 36 (5): 1320-1328

  Abstract

  PURPOSE: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. METHODS: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. RESULTS: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). CONCLUSION: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.

  View details for DOI 10.1007/s00270-013-0547-9

  View details for PubMedID 23354961

• Pilot Prospective Evaluation of Early Response to Bevacizumab Treatment Using the Novel PET/CT Radiopharmaceutical 18F FPPRGD2 Iagaru, A., Mosci, C., Davidzon, G., Kumar, M., Shen, B., Chin, F., Gambhir, S. S. SPRINGER. 2013: S185

  View details for Web of Science ID 000325853400290

• Imaging Tumor Angiogenesis: The Road to Clinical Utility AMERICAN JOURNAL OF ROENTGENOLOGY Iagaru, A., Gambhir, S. S. 2013; 201 (2): W183-W191

  Abstract

  OBJECTIVE. Tumor growth and progression require the formation of new blood vessels from preexisting vasculature, a process called angiogenesis. The ability to noninvasively visualize angiogenesis may provide new opportunities to more appropriately select patients for antiangiogenesis treatment and to monitor treatment efficacy. CONCLUSION. The superior molecular sensitivity of PET and the lack of radiation from MRI and contrast-enhanced ultrasound put these techniques at the forefront of clinical translation.

  View details for DOI 10.2214/AJR.12.8568

  View details for Web of Science ID 000322225400003

  View details for PubMedID 23883233

• An Observational Study of Circulating Tumor Cells and F-18-FDG PET Uptake in Patients with Treatment-Naive Non-Small Cell Lung Cancer PLOS ONE Nair, V. S., Keu, K. V., Luttgen, M. S., Kolatkar, A., Vasanawala, M., Kuschner, W., Bethel, K., Iagaru, A. H., Hoh, C., Shrager, J. B., Loo, B. W., Bazhenova, L., Nieva, J., Gambhir, S. S., Kuhn, P. 2013; 8 (7)

  Abstract

  We investigated the relationship of circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) with tumor glucose metabolism as defined by (18)F-fluorodeoxyglucose (FDG) uptake since both have been associated with patient prognosis.We performed a retrospective screen of patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell Adhesion Molecule (EpCAM) independent fluid biopsy based on cell morphology for CTC detection and enumeration (defined here as High Definition CTCs or "HD-CTCs"). We then correlated HD-CTCs with quantitative FDG uptake image data calibrated across centers in a cross-sectional analysis.We assessed seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile range, IQR, 2.0-3.6) and median maximum standardized uptake value (SUVmax) was 7.2 (IQR 3.7-15.5). More than 2 HD-CTCs were detected in 63% of patients, whether across all stages (45 of 71) or in stage I disease (27 of 43). HD-CTCs were weakly correlated with partial volume corrected tumor SUVmax (r = 0.27, p-value = 0.03) and not correlated with tumor diameter (r = 0.07; p-value = 0.60). For a given partial volume corrected SUVmax or tumor diameter there was a wide range of detected HD-CTCs in circulation for both early and late stage disease.CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, in vivo tumor biology in the early stages of this deadly disease.

  View details for DOI 10.1371/journal.pone.0067733

  View details for Web of Science ID 000321425300025

  View details for PubMedID 23861795

  View details for PubMedCentralID PMC3702496

• Pilot prospective evaluation of 99mTc-MDP scintigraphy, 18F NaF PET/CT, 18F FDG PET/CT and whole-body MRI for detection of skeletal metastases. Clinical nuclear medicine Iagaru, A., Young, P., Mittra, E., Dick, D. W., Herfkens, R., Gambhir, S. S. 2013; 38 (7): e290-6

  Abstract

  The aim of this study was to compare Tc-MDP bone scanning, F NaF PET/CT, F FDG PET/CT, and whole-body MRI (WBMRI) for detection of known osseous metastases.This prospective pilot trial (September 2007-April 2009) enrolled 10 participants (5 men, 5 women, 47-81 years old) diagnosed with cancer and known osseous metastases. F NaF PET/CT, F FDG PET/CT, and WBMRI were performed within 1 month for each participant.The image quality and evaluation of extent of disease were superior by F NaF PET/CT compared to Tc-MDP scintigraphy in all patients with skeletal lesions and compared to F FDG PET/CT in 3 of the patients with skeletal metastases. F NaF PET/CT showed osseous metastases where F FDG PET/CT was negative in another 3 participants. Extraskeletal metastases were identified by F FDG PET/CT in 6 participants. WBMRI with the combination of iterative decomposition of water and fat with echo asymmetry and least-squares estimation, short tau inversion recovery, and diffusion-weighted imaging pulse sequences showed fewer lesions than F NaF PET/CT in 5 patients, same number of lesions in 2 patients, and more lesions in 1 patient. WBMRI showed fewer lesions than F FDG in 3 patients and same lesions in 6 patients.Our pilot phase prospective trial demonstrated superior image quality and evaluation of skeletal disease extent with F NaF PET/CT compared to Tc-MDP scintigraphy and F FDG PET/CT, as well as the feasibility of multisequence WBMRI. In addition, F FDG PET/CT provided valuable soft-tissue information that can change disease management. Further evaluation of these findings using the recently introduced PET/MRI scanners is warranted.

  View details for DOI 10.1097/RLU.0b013e3182815f64

  View details for PubMedID 23455520

• Pilot prospective evaluation of 99mTc-MDP scintigraphy, 18F NaF PET/CT, 18F FDG PET/CT and whole-body MRI for detection of skeletal metastases. Clinical nuclear medicine Iagaru, A., Young, P., Mittra, E., Dick, D. W., Herfkens, R., Gambhir, S. S. 2013; 38 (7): e290-6

  View details for DOI 10.1097/RLU.0b013e3182815f64

  View details for PubMedID 23455520

• Utilizing SPECT/CT to improve small bowel transit studies Kulm, J., Iagaru, A., Quon, A. SOC NUCLEAR MEDICINE INC. 2013

  View details for Web of Science ID 000209478700138

• Biodistribution and kinetics of 18F FPPRGD2 in cancer patients Davidzon, G., Mosci, C., Mittra, E., Shen, B., Chin, F., Gambhir, S., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2013

  View details for Web of Science ID 000209478700012

• Developing a non-invasive, diagnostic test for stage I non-small cell lung cancer using circulating tumor cells. Luttgen, M. S., Keu, K., Nair, V. S., Horng, G., Vasanawala, M., Kolatkar, A., Carlsson, A., Sabouri, M., Loo, B. W., Shrager, J. B., Iagaru, A., Kuschner, W., Kuhn, P., Gambhir, S. S. AMER ASSOC CANCER RESEARCH. 2013

  View details for DOI 10.1158/1538-7445.AM2013-3485

  View details for Web of Science ID 000331220602190

• Second Sino-American Conference on Nuclear Medicine JOURNAL OF NUCLEAR MEDICINE Delbeke, D., Alessio, A., Iagaru, A. 2013; 54 (4): 15N-16N

  View details for Web of Science ID 000316939200001

  View details for PubMedID 23546927

• Combined F-18-Fluoride and F-18-FDG PET/CT Scanning for Evaluation of Malignancy: Results of an International Multicenter Trial JOURNAL OF NUCLEAR MEDICINE Iagaru, A., Mittra, E., Mosci, C., Dick, D. W., Sathekge, M., Prakash, V., Iyer, V., Lapa, P., Isidoro, J., de Lima, J. M., Gambhir, S. S. 2013; 54 (2): 176-183

  Abstract

  (18)F-FDG PET/CT is used in a variety of cancers, but because of variable rates of glucose metabolism, not all cancers are reliably identified. (18)F(-) PET/CT allows for the acquisition of highly sensitive and specific images of the skeleton. We prospectively evaluated combined (18)F(-)/(18)F-FDG as a single PET/CT examination for evaluation of cancer patients and compared it with separate (18)F(-) PET/CT and (18)F-FDG PET/CT scans.One hundred fifteen participants with cancer were prospectively enrolled in an international multicenter trial evaluating (18)F(-) PET/CT, (18)F-FDG PET/CT, and combined (18)F(-)/(18)F-FDG PET/CT. The 3 PET/CT scans were performed sequentially within 4 wk of one another for each patient.(18)F(-)/(18)F-FDG PET/CT allowed for accurate interpretation of radiotracer uptake outside the skeleton, with findings similar to those of (18)F-FDG PET/CT. In 19 participants, skeletal disease was more extensive on (18)F(-) PET/CT and (18)F(-)/(18)F-FDG PET/CT than on (18)F-FDG PET/CT. In another 29 participants, (18)F(-) PET/CT and (18)F(-)/(18)F-FDG PET/CT showed osseous metastases where (18)F-FDG PET/CT was negative. The extent of skeletal lesions was similar in 18 participants on all 3 scans.This trial demonstrated that combined (18)F(-)/(18)F-FDG PET/CT shows promising results when compared with separate (18)F(-) PET/CT and (18)F-FDG PET/CT for evaluation of cancer patients. This result opens the possibility for improved patient care and reduction in health-care costs, as will be further evaluated in future trials.

  View details for DOI 10.2967/jnumed.112.108803

  View details for Web of Science ID 000314691200016

  View details for PubMedID 23243299

• An observational study of circulating tumor cells and (18)F-FDG PET uptake in patients with treatment-naive non-small cell lung cancer. PloS one Nair, V. S., Keu, K. V., Luttgen, M. S., Kolatkar, A., Vasanawala, M., Kuschner, W., Bethel, K., Iagaru, A. H., Hoh, C., Shrager, J. B., Loo, B. W., Bazhenova, L., Nieva, J., Gambhir, S. S., Kuhn, P. 2013; 8 (7)

  Abstract

  We investigated the relationship of circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) with tumor glucose metabolism as defined by (18)F-fluorodeoxyglucose (FDG) uptake since both have been associated with patient prognosis.We performed a retrospective screen of patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell Adhesion Molecule (EpCAM) independent fluid biopsy based on cell morphology for CTC detection and enumeration (defined here as High Definition CTCs or "HD-CTCs"). We then correlated HD-CTCs with quantitative FDG uptake image data calibrated across centers in a cross-sectional analysis.We assessed seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile range, IQR, 2.0-3.6) and median maximum standardized uptake value (SUVmax) was 7.2 (IQR 3.7-15.5). More than 2 HD-CTCs were detected in 63% of patients, whether across all stages (45 of 71) or in stage I disease (27 of 43). HD-CTCs were weakly correlated with partial volume corrected tumor SUVmax (r = 0.27, p-value = 0.03) and not correlated with tumor diameter (r = 0.07; p-value = 0.60). For a given partial volume corrected SUVmax or tumor diameter there was a wide range of detected HD-CTCs in circulation for both early and late stage disease.CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, in vivo tumor biology in the early stages of this deadly disease.

  View details for DOI 10.1371/journal.pone.0067733

  View details for PubMedID 23861795

  View details for PubMedCentralID PMC3702496

• 18F-FDG PET/CT Demonstration of Diffuse Lymphohistiocytic Granulomatous Vasculitis. Clinical nuclear medicine Kumar, M. n., Iagaru, A. n. 2013

  Abstract

  Surveillance FDG PET/CT was performed in a 75-year-old woman with history of melanoma and colon cancer. She had rash and erythematous papules on the forearms, elbows, knees, and thighs and then developed right-leg weakness, difficulty with fine motor movement, and ptosis. Chest CT identified a right-lung spiculated nodule. Skin and pulmonary nodule biopsies showed lymphohistiocytic infiltrate with granulomatous features, without lymphoid cells, metastatic carcinoma or melanoma cells, or microorganisms. Epstein-Barr immunostain result was negative, making lymphomatoid granuloma unlikely. The inflammatory process involved the peripheral vasculature on FDG PET, and given the related neuropathy, findings were compatible with granulomatous vasculitis.

  View details for PubMedID 23510876

• Initial investigation of F-18-NaF PET/CT for identification of vertebral sites amenable to surgical revision after spinal fusion surgery EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Quon, A., Dodd, R., Iagaru, A., de Abreu, M. R., Hennemann, S., Alves Neto, J. M., Sprinz, C. 2012; 39 (11): 1737-1744

  Abstract

  A pilot study was performed in patients with recurrent back pain after spinal fusion surgery to evaluate the ability of (18)F-NaF PET/CT imaging to correctly identify those requiring surgical intervention and to locate a site amenable to surgical intervention.In this prospective study 22 patients with recurrent back pain after spinal surgery and with equivocal findings on physical examination and CT were enrolled for evaluation with (18)F-NaF PET/CT. All PET/CT images were prospectively reviewed with the primary objective of identifying or ruling out the presence of lesions amenable to surgical intervention. The PET/CT results were then validated during surgical exploration or clinical follow-up of at least 15 months.Abnormal (18)F-NaF foci were found in 16 of the 22 patients, and surgical intervention was recommended. These foci were located at various sites: screws, cages, rods, fixation hardware, and bone grafts. In 6 of the 22 patients no foci requiring surgical intervention were found. Validation of the results by surgery (15 patients) or on clinical follow-up (7 patients) showed that (18)F-NaF PET/CT correctly predicted the presence of an abnormality requiring surgical intervention in 15 of 16 patients and was falsely positive in 1 of 16.In this initial investigation, (18)F-NaF PET/CT imaging showed potential utility for evaluation of recurrent symptoms after spinal fusion surgery by identifying those patients requiring surgical management.

  View details for DOI 10.1007/s00259-012-2196-7

  View details for Web of Science ID 000309562600010

  View details for PubMedID 22895860

  View details for PubMedCentralID PMC3464378

• Positron Emission Tomography of Cu-64-DOTA-Rituximab in a Transgenic Mouse Model Expressing Human CD20 for Clinical Translation to Image NHL MOLECULAR IMAGING AND BIOLOGY Natarajan, A., Gowrishankar, G., Nielsen, C. H., Wang, S., Iagaru, A., Goris, M. L., Gambhir, S. S. 2012; 14 (5): 608-616

  Abstract

  This study aims to evaluate (64)Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation.(64)Cu was chelated to DOTA-rituximab. Multiple radiolabeling, quality assurance, and imaging experiments were performed. The human CD20 antigen was expressed in B cells of transgenic mice (CD20TM). The mice groups studied were: (a) control (nude mice, n = 3) that received 7.4 MBq/dose, (b) with pre-dose (CD20TM, n = 6) received 2 mg/kg pre-dose of cold rituximab prior to PETRIT of 7.4 MBq/dose, and (c) without pre-dose (CD20TM, n = 6) PETRIT alone received 7.4 MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs.PETRIT was obtained with a specific activity of 545 ± 38.91 MBq/nmole, radiochemical purity >95%, and immunoreactivity >75%. At 24 h, spleenic uptake of PETRIT%ID/g (mean ± STD) with and without pre-dose was 1.76 ± 0.43% and 16.5 ± 0.45%, respectively (P value = 0.01). Liver uptake with and without pre-dose was 0.41 ± 0.51% and 0.52 ± 0.17% (P value = 0.86), respectively. The human equivalents of highest dose organs with and without pre-dose are osteogenic cells at 30.8 ± 0.4 μSv/MBq and the spleen at 99 ± 4 μSv/MBq, respectively.PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non-Hodgkins lymphoma patients.

  View details for DOI 10.1007/s11307-011-0537-8

  View details for Web of Science ID 000308819300011

  View details for PubMedID 22231277

• Metabolic Imaging Patterns of Complete Local Response to Chemoradiation in Patients with Nasopharyngeal Carcinoma: A Review Keu, K., Mittra, E., Iagaru, A. SPRINGER. 2012: S558

  View details for Web of Science ID 000309726603242

• Post-Surgical 131I Ablation in Patients with Papillary Thyroid Cancer: The Role of Diagnostic 123I Whole Body Scan Iagaru, A., Mosci, C., Akatsu, H., Basina, M., Dosiou, C., McDougall, I. SPRINGER. 2012: S235

  View details for Web of Science ID 000309726600290

• alpha v beta 3 Integrins as a Biomarker of Disease Recurrence in Glioblastoma Multiforme: Initial Clinical Results Using 18F FPPRGD2 PET/CT 4th International Symposium on Targeted Radiotherapy and Dosimetry (ISTARD) in Conjunction with the 25th Annual Congress of the European-Association-of-Nuclear-Medicine (EANM) Iagaru, A., Mosci, C., Mittra, E. S., Shin, B., Chin, F., Gambhir, S. S. SPRINGER. 2012: S244–S245

  View details for Web of Science ID 000309726600324

• The Impact of Partial Volume Correction in the Evaluation of Solitary Pulmonary Nodules by FDG PET/CT in a Population at Intermediate Risk of Lung Cancer 4th International Symposium on Targeted Radiotherapy and Dosimetry (ISTARD) in Conjunction with the 25th Annual Congress of the European-Association-of-Nuclear-Medicine (EANM) Keu, K., Nair, V. S., Mittra, E., Gambhir, S. S., Iagaru, A. SPRINGER. 2012: S455–S455

  View details for Web of Science ID 000309726602293

• F-18-FDG PET/CT Demonstration of a Liver Metastasis in a Patient With Papillary Thyroid Cancer CLINICAL NUCLEAR MEDICINE Mosci, C., McDougall, I. R., Jeffrey, R. B., Iagaru, A. 2012; 37 (9): E234-E236

  Abstract

  A 51-year-old woman with papillary thyroid cancer had recurrent disease. An unexpected FDG-avid hepatic metastasis was identified. Follow-up contrast-enhanced CT scan showed a hepatic lesion, compatible with malignancy. Histopathologic examination demonstrated metastatic carcinoma, consistent with thyroid primary. Few studies reported liver metastases originating from thyroid cancer on FDG PET. These were medullary thyroid carcinomas (MTC) or poorly differentiated cancers. There are no reports describing liver metastasis from PTC diagnosed by FDG PET/CT.

  View details for DOI 10.1097/RLU.0b013e318262ae07

  View details for Web of Science ID 000307808000007

  View details for PubMedID 22889801

• Validation that metabolic tumor volume predicts outcome in head-and-neck cancer. International journal of radiation oncology, biology, physics Tang, C., Murphy, J. D., Khong, B., La, T. H., Kong, C., Fischbein, N. J., Colevas, A. D., Iagaru, A. H., Graves, E. E., Loo, B. W., Le, Q. 2012; 83 (5): 1514-1520

  Abstract

  We have previously reported that metabolic tumor volume (MTV) obtained from pretreatment (18)F-fluorodeoxydeglucose positron emission tomography (FDG PET)/ computed tomography (CT) predicted outcome in patients with head-and-neck cancer (HNC). The purpose of this study was to validate these results on an independent dataset, determine whether the primary tumor or nodal MTV drives this correlation, and explore the interaction with p16(INK4a) status as a surrogate marker for human papillomavirus (HPV).The validation dataset in this study included 83 patients with squamous cell HNC who had a FDG PET/CT scan before receiving definitive radiotherapy. MTV and maximum standardized uptake value (SUV(max)) were calculated for the primary tumor, the involved nodes, and the combination of both. The primary endpoint was to validate that MTV predicted progression-free survival and overall survival. Secondary analyses included determining the prognostic utility of primary tumor vs. nodal MTV.Similarly to our prior findings, an increase in total MTV of 17 cm(3) (difference between the 75th and 25th percentiles) was associated with a 2.1-fold increase in the risk of disease progression (p = 0.0002) and a 2.0-fold increase in the risk of death (p = 0.0048). SUV(max) was not associated with either outcome. Primary tumor MTV predicted progression-free (hazard ratio [HR] = 1.94; p < 0.0001) and overall (HR = 1.57; p < 0.0001) survival, whereas nodal MTV did not. In addition, MTV predicted progression-free (HR = 4.23; p < 0.0001) and overall (HR = 3.21; p = 0.0029) survival in patients with p16(INK4a)-positive oropharyngeal cancer.This study validates our previous findings that MTV independently predicts outcomes in HNC. MTV should be considered as a potential risk-stratifying biomarker in future studies of HNC.

  View details for DOI 10.1016/j.ijrobp.2011.10.023

  View details for PubMedID 22270174

• Validation that Metabolic Tumor Volume Predicts Outcome in Head-and-Neck Cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Tang, C., Murphy, J. D., Khong, B., La, T. H., Kong, C., Fischbein, N. J., Colevas, A. D., Iagaru, A. H., Graves, E. E., Loo, B. W., Quynh-Thu Le, Q. T. 2012; 83 (5): 1514-1520

  Abstract

  We have previously reported that metabolic tumor volume (MTV) obtained from pretreatment (18)F-fluorodeoxydeglucose positron emission tomography (FDG PET)/ computed tomography (CT) predicted outcome in patients with head-and-neck cancer (HNC). The purpose of this study was to validate these results on an independent dataset, determine whether the primary tumor or nodal MTV drives this correlation, and explore the interaction with p16(INK4a) status as a surrogate marker for human papillomavirus (HPV).The validation dataset in this study included 83 patients with squamous cell HNC who had a FDG PET/CT scan before receiving definitive radiotherapy. MTV and maximum standardized uptake value (SUV(max)) were calculated for the primary tumor, the involved nodes, and the combination of both. The primary endpoint was to validate that MTV predicted progression-free survival and overall survival. Secondary analyses included determining the prognostic utility of primary tumor vs. nodal MTV.Similarly to our prior findings, an increase in total MTV of 17 cm(3) (difference between the 75th and 25th percentiles) was associated with a 2.1-fold increase in the risk of disease progression (p = 0.0002) and a 2.0-fold increase in the risk of death (p = 0.0048). SUV(max) was not associated with either outcome. Primary tumor MTV predicted progression-free (hazard ratio [HR] = 1.94; p < 0.0001) and overall (HR = 1.57; p < 0.0001) survival, whereas nodal MTV did not. In addition, MTV predicted progression-free (HR = 4.23; p < 0.0001) and overall (HR = 3.21; p = 0.0029) survival in patients with p16(INK4a)-positive oropharyngeal cancer.This study validates our previous findings that MTV independently predicts outcomes in HNC. MTV should be considered as a potential risk-stratifying biomarker in future studies of HNC.

  View details for DOI 10.1016/j.ijrobp.2011.10.023

  View details for Web of Science ID 000306128100046

  View details for PubMedCentralID PMC3337958

• Prognostic Value of Metabolic Tumor Volume and Velocity in Predicting Head-and-Neck Cancer Outcomes INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Chu, K. P., Murphy, J. D., La, T. H., Krakow, T. E., Iagaru, A., Graves, E. E., Hsu, A., Maxim, P. G., Loo, B., Chang, D. T., Quynh-Thu Le, Q. T. 2012; 83 (5): 1521-1527

  Abstract

  We previously showed that metabolic tumor volume (MTV) on positron emission tomography-computed tomography (PET-CT) predicts for disease recurrence and death in head-and-neck cancer (HNC). We hypothesized that increases in MTV over time would correlate with tumor growth and biology, and would predict outcome. We sought to examine tumor growth over time in serial pretreatment PET-CT scans.From 2006 to 2009, 51 patients had two PET-CT scans before receiving HNC treatment. MTV was defined as the tumor volume ≥ 50% of maximum SUV (SUV(max)). MTV was calculated for the primary tumor, nodal disease, and composite (primary tumor + nodes). MTV and SUV velocity were defined as the change in MTV or SUV(max) over time, respectively. Cox regression analyses were used to examine correlations between SUV, MTV velocity, and outcome (disease progression and overall survival).The median follow-up time was 17.5 months. The median time between PET-CT scans was 3 weeks. Unexpectedly, 51% of cases demonstrated a decrease in SUV(max) (average, -0.1 cc/week) and MTV (average, -0.3 cc/week) over time. Despite the variability in MTV, primary tumor MTV velocity predicted disease progression (hazard ratio 2.94; p = 0.01) and overall survival (hazard ratio 1.85; p = 0.03).Primary tumor MTV velocity appears to be a better prognostic indicator of disease progression and survival in comparison to nodal MTV velocity. However, substantial variability was found in PET-CT biomarkers between serial scans. Caution should be used when PET-CT biomarkers are integrated into clinical protocols for HNC.

  View details for DOI 10.1016/j.ijrobp.2011.10.022

  View details for PubMedID 22270168

• (18)F NaF PET/CT in the Assessment of Malignant Bone Disease. PET clinics Mosci, C., Iagaru, A. 2012; 7 (3): 263-274

  Abstract

  Diagnostic imaging plays a major role in the evaluation of patients with malignant bone disease. (18)F-Labeled sodium fluoride ((18)F NaF) is a positron-emitting radiopharmaceutical with desirable characteristics (rapid blood clearance and bone uptake) for high-quality functional imaging of the skeleton. In addition to higher sensitivity and specificity, (18)F NaF PET combined with computed tomography (PET/CT) allows for shorter imaging time, thus improving patients' convenience and benefiting the overall workflow of the imaging facility. Although as yet no robust evidence-based data exist, this article summarizes the published data currently available on the role of (18)F NaF PET/CT in the assessment of malignant bone disease.

  View details for DOI 10.1016/j.cpet.2012.04.003

  View details for PubMedID 27157457

• Correlating circulating tumor cells with F-18-FDG positron emission tomography (PET) uptake in patients with treatment naive non-small cell lung cancer: A pilot study Kuhn, P., Keu, K., Nair, V. S., Luttgen, M., Maestas, S., Bethel, K., Souder, K., Vasanawala, M., Kuschner, W., Iagaru, A. H., Hoh, C., Nieva, J., Bazhenova, L., Gambhir, S. S. AMER ASSOC CANCER RESEARCH. 2012

  View details for DOI 10.1158/1538-7445.AM2012-2369

  View details for Web of Science ID 000209701505199

• Prospective Evaluation of Tc-99m MDP Scintigraphy, F-18 NaF PET/CT, and F-18 FDG PET/CT for Detection of Skeletal Metastases MOLECULAR IMAGING AND BIOLOGY Iagaru, A., Mittra, E., Dick, D. W., Gambhir, S. S. 2012; 14 (2): 252-259

  Abstract

  Technetium (Tc) methylene diphosphonate (MDP) has been the standard method for bone scintigraphy for three decades. (18)F sodium fluoride ((18)F NaF) positron emission tomography (PET)/computed tomography (CT) has better resolution and is considered superior. The role of 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F FDG) PET/CT is proven in a variety of cancers, for which it has changed the practice of oncology. There are few prospective studies comparing these three methods of detection of skeletal metastases. Thus, we were prompted to initiate this prospective pilot trial.This is a prospective study (Sep 2007-Dec 2010) of 52 patients with proven malignancy referred for evaluation of skeletal metastases. There were 37 men and 15 women, 19-84 years old (average, 55.6 ± 15.9). Technetium-99m ((99m)Tc) MDP bone scintigraphy, (18)F NaF PET/CT, and (18)F FDG PET/CT were subsequently performed within 1 month.Skeletal lesions were detected by (99m)Tc MDP bone scintigraphy in 22 of 52 patients, by (18)F NaF PET/CT in 24 of 52 patients, and by (18)F FDG PET/CT in 16 of 52 patients. The image quality and evaluation of extent of disease were superior by (18)F NaF PET/CT over (99m)Tc MDP scintigraphy in all 22 patients with skeletal lesions on both scans and over (18)F FDG PET/CT in 11 of 16 patients with skeletal metastases on (18)F FDG PET/CT. In two patients, (18)F NaF PET/CT showed skeletal metastases not seen on either of the other two scans. Extraskeletal lesions were identified by (18)F FDG PET/CT in 28 of 52 subjects.Our prospective pilot-phase trial demonstrates superior image quality and evaluation of skeletal disease extent with (18)F NaF PET/CT over (99m)Tc MDP scintigraphy and (18)F FDG PET/CT. At the same time, (18)F FDG PET detects extraskeletal disease that can significantly change disease management. As such, a combination of (18)F FDG PET/CT and (18)F NaF PET/CT may be necessary for cancer detection. Additional evaluation with larger cohorts is required to confirm these preliminary findings.

  View details for DOI 10.1007/s11307-011-0486-2

  View details for Web of Science ID 000301584100013

  View details for PubMedID 21479710

• Demonstration of peripheral nerve root involvement by non-Hodgkin's lymphoma on F-18-FDG PET/CT EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Guo, H., Mosci, C., Iagaru, A. 2012; 39 (4): 729-730

  View details for DOI 10.1007/s00259-011-2000-0

  View details for Web of Science ID 000302287500024

  View details for PubMedID 22124779

• Prospective comparison of combined F-18-FDG and F-18-NaF PET/CT vs. F-18-FDG PET/CT imaging for detection of malignancy EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Lin, F. I., Rao, J. E., Mittra, E. S., Nallapareddy, K., Chengapa, A., Dick, D. W., Gambhir, S. S., Iagaru, A. 2012; 39 (2): 262-270

  Abstract

  Typically, (18)F-FDG PET/CT and (18)F-NaF PET/CT scans are done as two separate studies on different days to allow sufficient time for the radiopharmaceutical from the first study to decay. This is inconvenient for the patients and exposes them to two doses of radiation from the CT component of the examinations. In the current study, we compared the clinical usefulness of a combined (18)F-FDG/(18)F-NaF PET/CT scan with that of a separate (18)F-FDG-only PET/CT scan.There were 62 patients enrolled in this prospective trial. All had both an (18)F-FDG-alone PET/CT scan and a combined (18)F-FDG/(18)F-NaF PET/CT scan. Of the 62 patients, 53 (85%) received simultaneous tracer injections, while 9 (15%) received (18)F-NaF subsequent to the initial (18)F-FDG dose (average delay 2.2 h). Images were independently reviewed for PET findings by two Board-Certified nuclear medicine physicians, with discrepancies resolved by a third reader. Interpreters were instructed to only report findings that were concerning for malignancy. Reading the (18)F-FDG-only scan first for half of the patients controlled for order bias.In 15 of the 62 patients (24%) neither the (18)F-FDG-only PET/CT scan nor the combined (18)F-FDG/(18)F-NaF PET/CT scan identified malignancy. In the remaining 47 patients who had PET findings of malignancy, a greater number of lesions were detected in 16 of 47 patients (34%) using the combined (18)F-FDG/(18)F-NaF PET/CT scan compared to the (18)F-FDG-only PET/CT scan. In 2 of these 47 patients (4%), the (18)F-FDG-only scan demonstrated soft tissue lesions that were not prospectively identified on the combined study. In 29 of these 47 patients (62%), the combined scan detected an equal number of lesions compared to the (18)F-FDG-only scan. Overall, 60 of all the 62 patients (97%) showed an equal or greater number of lesions on the combined scan than on the (18)F-FDG-only scan.The current study demonstrated that (18)F-FDG and (18)F-NaF can be combined in a single PET/CT scan by administering the two radiopharmaceuticals simultaneously or in sequence on the same day. In addition to patient convenience and reduced radiation exposure from the CT component, the combined (18)F-FDG/(18)F-NaF PET/CT scan appeared to increase the sensitivity for detection of osseous lesions compared to the (18)F-FDG-only PET/CT scan in the studied population.

  View details for DOI 10.1007/s00259-011-1971-1

  View details for Web of Science ID 000302286600009

  View details for PubMedID 22065013

• Response to Intra-Arterial Oncolytic Virotherapy with the Herpes Virus NV1020 Evaluated by [F-18]Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography HUMAN GENE THERAPY Sze, D. Y., Iagaru, A. H., Gambhir, S. S., de Haan, H. A., Reid, T. R. 2012; 23 (1): 91-97

  Abstract

  Oncolytic virotherapy poses unique challenges to the evaluation of tumor response. We hypothesized that the addition of [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) to standard computed tomography (CT) evaluation would improve diagnostic and prognostic power of the measurement of tumor response to oncolytic virotherapy. A phase I/II trial was conducted to investigate treatment of hepatic metastases from colorectal carcinoma using intra-arterial administration of the oncolytic herpes virus NV1020. Both contrast-enhanced CT and FDG PET were obtained on each patient at each time point. Quantitative FDG PET and CT responses were correlated with each other and with clinical outcome metrics. A majority of patients showed initial post-viral infusion increases in tumor size (69%) or in standardized uptake value (SUV) (80%) large enough to qualify as progressive disease. Most showed subsequent decreases in tumor size (64%) or SUV (83%) enough to be reclassified as partial response or stable disease. Late PET and CT imaging results correlated well with each other and with clinical outcomes, but results from early in the treatment scheme did not correlate with each other, with later results, or with clinical outcomes. The addition of FDG PET to the evaluation of tumor response to the oncolytic virus NV1020 did not provide useful diagnostic or prognostic data. More sophisticated molecular imaging will need to be developed to monitor the effects of this novel class of antineoplastic agents.

  View details for DOI 10.1089/hum.2011.141

  View details for Web of Science ID 000299604000011

  View details for PubMedID 21895536

• Correlation between metabolic tumor volume and pathologic tumor volume in squamous cell carcinoma of the oral cavity RADIOTHERAPY AND ONCOLOGY Murphy, J. D., Chisholm, K. M., Daly, M. E., Wiegner, E. A., Truong, D., Iagaru, A., Maxim, P. G., Loo, B. W., Graves, E. E., Kaplan, M. J., Kong, C., Le, Q. 2011; 101 (3): 356-361

  Abstract

  To explore the relationship between pathologic tumor volume and volume estimated from different tumor segmentation techniques on (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in oral cavity cancer.Twenty-three patients with squamous cell carcinoma of the oral tongue had PET-CT scans before definitive surgery. Pathologic tumor volume was estimated from surgical specimens. Metabolic tumor volume (MTV) was defined from PET-CT scans as the volume of tumor above a given SUV threshold. Multiple SUV thresholds were explored including absolute SUV thresholds, relative SUV thresholds, and gradient-based techniques.Multiple MTV's were associated with pathologic tumor volume; however the correlation was poor (R(2) range 0.29-0.58). The ideal SUV threshold, defined as the SUV that generates an MTV equal to pathologic tumor volume, was independently associated with maximum SUV (p=0.0005) and tumor grade (p=0.024). MTV defined as a function of maximum SUV and tumor grade improved the prediction of pathologic tumor volume (R(2)=0.63).Common SUV thresholds fail to predict pathologic tumor volume in head and neck cancer. The optimal technique that allows for integration of PET-CT with radiation treatment planning remains to be defined. Future investigation should incorporate biomarkers such as tumor grade into definitions of MTV.

  View details for DOI 10.1016/j.radonc.2011.05.040

  View details for PubMedID 21665308

• PET/CT Imaging of Thyroid Cancer CLINICAL NUCLEAR MEDICINE Mosci, C., Iagaru, A. 2011; 36 (12): E180-E185

  Abstract

  Positron emission tomography (PET) is a highly sensitive, low invasive technology for cancer biology imaging. The role of F-18 FDG PET/CT in differentiated thyroid cancer (DTC) is well established, particularly in patients presenting with elevated Tg levels and negative radioactive iodine WBS. It has been demonstrated that F-18 FDG uptake represents less differentiated thyroid cancer cells or dedifferentiated cells and PET positive lesions are more likely to be resistant to I treatment. The uptake of F-18 FDG is related to tumor size, thyroid capsule invasion and histological variants with a poor prognosis. As in other cancers, early detection of recurrences improves outcomes and survival. I PET/CT can also be used to image the patients with DTC, similarly to I WBS. Compared with F-18 FDG PET/CT, its spatial resolution is only slightly degraded but increasing the imaging time reduces this difference. In addition, F-18 FDG PET/CT has been found helpful in the management of patients with anaplastic and medullary thyroid cancer. Other radiopharmaceuticals such as Ga-DOTATOC and F-18 DOPA may provide complimentary information to F-18 FDG PET/CT in the detection of recurrent thyroid cancer.

  View details for DOI 10.1097/RLU.0b013e3182291d03

  View details for Web of Science ID 000296796800001

  View details for PubMedID 22064103

• Pilot Pharmacokinetic and Dosimetric Studies of F-18-FPPRGD2: A PET Radiopharmaceutical Agent for Imaging alpha(v)beta(3) Integrin Levels RADIOLOGY Mittra, E. S., Goris, M. L., Iagaru, A. H., Kardan, A., Burton, L., Berganos, R., Chang, E., Liu, S., Shen, B., Chin, F. T., Chen, X., Gambhir, S. S. 2011; 260 (1): 182-191

  Abstract

  To assess the safety, biodistribution, and dosimetric properties of the positron emission tomography (PET) radiopharmaceutical agent fluorine 18 ((18)F) FPPRGD2 (2-fluoropropionyl labeled PEGylated dimeric RGD peptide [PEG3-E{c(RGDyk)}2]), which is based on the dimeric arginine-glycine-aspartic acid (RGD) peptide sequence and targets α(v)β(3) integrin, in the first volunteers imaged with this tracer.The protocol was approved by the institutional review board, and written informed consent was obtained from all participants. Five healthy volunteers underwent whole-body combined PET-computed tomography 0.5, 1.0, 2.0, and 3.0 hours after tracer injection (mean dose, 9.5 mCi ± 3.4 [standard deviation] [351.5 MBq ± 125.8]; mean specific radioactivity, 1200 mCi/mmol ± 714 [44.4 GBq/mmol ± 26.4]). During this time, standard vital signs, electrocardiographic (ECG) readings, and blood sample values (for chemistry, hematologic, and liver function tests) were checked at regular intervals and 1 and 7 days after the injection. These data were used to evaluate tracer biodistribution and dosimetric properties, time-activity curves, and the stability of laboratory values. Significant changes in vital signs and laboratory values were evaluated by using a combination of population-averaged generalized estimating equation regression and exact paired Wilcoxon tests.The administration of (18)F-FPPRGD2 was well tolerated, with no marked effects on vital signs, ECG readings, or laboratory values. The tracer showed the same pattern of biodistribution in all volunteers: primary clearance through the kidneys (0.360 rem/mCi ± 0.185 [0.098 mSv/MBq ± 0.050]) and bladder (0.862 rem/mCi ± 0.436 [0.233 mSv/MBq ± 0.118], voiding model) and uptake in the spleen (0.250 rem/mCi ± 0.168 [0.068 mSv/MBq ± 0.046]) and large intestine (0.529 rem/mCi ± 0.236 [0.143 mSv/MBq ± 0.064]). The mean effective dose of (18)F-FPPRGD2 was 0.1462 rem/mCi ± 0.0669 (0.0396 mSv/MBq ± 0.0181). With an injected dose of 10 mCi (370 MBq) and a 1-hour voiding interval, a patient would be exposed to an effective radiation dose of 1.5 rem (15 mSv). Above the diaphragm, there was minimal uptake in the brain ventricles, salivary glands, and thyroid gland. Time-activity curves showed rapid clearance from the vasculature, with a mean 26% ± 17 of the tracer remaining in the circulation at 30 minutes and most of the activity occurring in the plasma relative to cells (mean whole blood-plasma ratio, 0.799 ± 0.096).(18)F-FPPRGD2 has desirable pharmacokinetic and biodistribution properties. The primary application is likely to be PET evaluation of oncologic patients-especially those with brain, breast, or lung cancer. Specific indications may include tumor staging, identifying patients who would benefit from antiangiogenesis therapy, and separating treatment responders from nonresponders early.

  View details for DOI 10.1148/radiol.11101139

  View details for Web of Science ID 000291932300021

  View details for PubMedID 21502381

  View details for PubMedCentralID PMC3121013

• FDG-PET/CT in Cancers of the Head and Neck: What is the Definition of Whole Body Scanning? MOLECULAR IMAGING AND BIOLOGY Iagaru, A., Mittra, E. S., Gambhir, S. S. 2011; 13 (2): 362-367

  Abstract

  The role of 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography (FDG-PET) was studied in a variety of cancers, including head and neck squamous cell carcinomas (HNSCC) and nasopharyngeal carcinomas (NPC), with several presentations indicating that for these clinical entities a "whole-body" (i.e., eyes to thighs) may yield little additional information. Therefore, we were prompted to review our experience with PET/computed tomography (CT) in the management of patients with HNSCC and NPC.This is a retrospective study of 133 patients with HNSCC, 23-90 years old (average: 58.2 ± 12.7) and 26 patients with NPC, ages 16-75 (average: 47.3 ± 17.1), who had whole body PET/CT at our institution from Jan 2003 to Nov 2006. Reinterpretation of the imaging studies for accuracy and data analysis from medical records was performed. Lesions identified on PET/CT below the level of the adrenal glands were recorded and tabulated.Lesions were identified below the adrenal glands in seven patients (5.2%) with HNSCC. These included hepatic and osseous metastases from HNSCC in two patients (1.5%), a new renal cancer (0.75%), a new pancreatic cancer (0.75%), a new colon cancer (0.75%) and findings proven benign on follow-up (focal colon uptake in one patient and an inflammatory inguinal lymph node in another patient; 1.5%). Lesions were identified below the adrenal glands in three patients (11.5%) with NPC. These included osseous metastases from NPC in two patients (7.7%) and findings proven benign on follow-up (focal colon uptake in one patient; 3.84%).This study suggests that whole body PET/CT imaging in HNSCC has a relatively low yield (3%, 95% CI: 1.33-8.42) of significant findings below the level of the adrenal glands. Therefore, implementing a more limited protocol (through the level of adrenal glands), especially in low-risk cases of HNSCC, may be considered. However, whole body PET/CT imaging in NPC may have a significant yield (7.7%, 95% CI: 1.02-25.26) of medically relevant findings below the level of the adrenal glands. Thus, the whole body (i.e., vertex to thighs) PET/CT scan of NPC patients appears to be the appropriate imaging protocol for this population. This recommendation requires further evaluation and validation in larger prospective studies.

  View details for DOI 10.1007/s11307-010-0343-8

  View details for Web of Science ID 000288177700021

  View details for PubMedID 20495879

• Thyroid Stunning: Fact or Fiction? SEMINARS IN NUCLEAR MEDICINE McDougall, I. R., Iagaru, A. 2011; 41 (2): 105-112

  Abstract

  Stunning of thyroid tissue by diagnostic activities of (131)I has been described by some investigators and refuted by others. The support both for and against stunning has at times been enthusiastic and vigorous. We present the data from both sides of the debate in an attempt to highlight the strengths and deficiencies in the investigations cited. Clinical, animal, and in vitro studies are included. There are considerable differences in clinical practice, such as the administered activity for diagnostic whole-body scan, delay between diagnostic scan and treatment, time between treatment and posttherapy scanning, and timing of follow-up studies, that have to be analyzed with care. Other factors that often cannot be judged, such as levels of thyroid-stimulating hormone and serum iodine at time of diagnostic testing versus treatment could have an influence on stunning. Larger diagnostic doses and longer delays to therapy appear to increase the likelihood of stunning. The stunning effect of early-absorbed radiation from the therapy should also be considered.

  View details for DOI 10.1053/j.semnuclmed.2010.10.004

  View details for Web of Science ID 000287263600006

  View details for PubMedID 21272684

• Case 166: Metastatic Left Pulmonary Artery Sarcoma RADIOLOGY Mittra, E. S., Iagaru, A. H., Leung, A. N. 2011; 258 (2): 645-648

  View details for DOI 10.1148/radiol.10082169

  View details for Web of Science ID 000286653700037

  View details for PubMedID 21273527

• (18)F-FDG PET/CT: timing for evaluation of response to therapy remains a clinical challenge. American journal of nuclear medicine and molecular imaging Iagaru, A. 2011; 1 (1): 63-64

  Abstract

  Utilizing novel imaging modalities for defining response and predicting long-term outcome after treatment may have a significant impact on cancer patient management. (18)F-FDG PET/CT has great potential for use in early assessment of response to cancer therapy. However, the lack of a general consensus on a specific set of response criteria makes adoption of PET difficult for the oncology community. The optimal time after initiating therapy for assessing response to treatment also has yet to be clearly determined.

  View details for PubMedID 23133796

• Current concepts and future directions in radioimmunotherapy. Current drug discovery technologies Lin, F. I., Iagaru, A. 2010; 7 (4): 253-262

  Abstract

  Radioimmunotherapy relies on the principles of immunotherapy, but expands the cytotoxic effects of the antibody by complexing it with a radiation-emitting particle. If we consider radioimmunotherapy as a step beyond immunotherapy of cancer, the step was prompted by the (relative) failure of the latter. The conventional way to explain the failure is a lack of intrinsic killing effect and a lack of penetration into poorly vascularized tumor masses. The addition of a radioactive label (usually a β-emitter) to the antibody would improve both. Radiation is lethal and the type of radiation used (beta rays) has a sufficient range to overcome the lack of antibody penetration. At present, the most successful (and FDA approved) radioimmunotherapy agents for lymphomas are anti-CD20 monoclonal antibodies. Rituximab (Rituxan(®)) is a chimeric antibody, used as a non-radioactive antibody and to pre-load the patient when Zevalin(®) is used. Zevalin(®) is the Yttrium-90 ((90)Y) or Indium-111 ((111)In) labeled form of Ibritumomab Tiuxetan. Bexxar(®) is the Iodine-131 ((131)I) labeled form of Tositumomab. Ibritumomab Tiuxetan and Tositumomab are murine anti-CD20 monoclonal antibodies, not chimeric antibodies. Promising research is being done to utilize radioimmunotherapy earlier in the treatment algorithm for lymphoma, including as initial, consolidation, and salvage therapies. However, despite more than 8 years since initial regulatory approval, radioimmunotherapy still has not achieved widespread use due to a combination of medical, scientific, logistic, and financial barriers. Other experimental uses for radioimmunotherapy include other solid tumors to treat infections. Optimization can potentially be done with pre-targeting and bi-specific antibodies. Alpha particle and Auger electron emitters show promise as future radioimmunotherapy agents but are mostly still in pre-clinical stages.

  View details for PubMedID 21034409

• [F-18]FPPRGD2 PET/CT Imaging of Integrin Expression in Healthy Volunteers 23rd Annual Congress of the European-Association-of-Nuclear-Medicine (EANM) Mittra, E., Iagaru, A., Goris, M. L., Chin, F., Chen, X., Gambhir, S. S. SPRINGER. 2010: S287–S287

  View details for Web of Science ID 000283023800400

• Combined F-18 Fluoride and F-18 FDG PET/CT Scan for Evaluation of Malignancy: Beyond the Pilot Phase Study 23rd Annual Congress of the European-Association-of-Nuclear-Medicine (EANM) Iagaru, A., Mittra, E., Dick, D. W., Gambhir, S. S. SPRINGER. 2010: S200–S200

  View details for Web of Science ID 000283023800010

• Tumor Measurements by F-18-FDG PET: How Accurate are they? 23rd Annual Congress of the European-Association-of-Nuclear-Medicine (EANM) Mittra, E., Iagaru, A., Gambhir, S. S. SPRINGER. 2010: S330–S331

  View details for Web of Science ID 000283023800598

• F-18 FDG PET/CT Demonstration of Lymphohistiocytic Meningitis CLINICAL NUCLEAR MEDICINE Mansouri, M. A., Iagaru, A. 2010; 35 (8): 633-634

  View details for Web of Science ID 000279892100023

  View details for PubMedID 20631522

• (18)F-FDG-PET and PET/CT for Evaluating Primary Bone Tumors. PET clinics Mittra, E., Iagaru, A. 2010; 5 (3): 327-339

  Abstract

  Imaging is critical for the proper evaluation of patients with primary tumors of bone. There is a growing role for (18)F-fluorodeoxyglucose PET and PET/computed tomography (CT) in the grading, staging, prognostication, evaluation of therapeutic response, and detection of recurrent disease in bone. These modalities can also be used to help differentiate benign from malignant disorders of bone.

  View details for DOI 10.1016/j.cpet.2010.04.004

  View details for PubMedID 27157837

• I-131-Tositumomab (BexxarA (R)) vs. Y-90-Ibritumomab (ZevalinA (R)) Therapy of Low-Grade Refractory/Relapsed Non-Hodgkin Lymphoma MOLECULAR IMAGING AND BIOLOGY Iagaru, A., Mittra, E. S., Ganjoo, K., Knox, S. J., Goris, M. L. 2010; 12 (2): 198-203

  Abstract

  The American Cancer Society estimated 66,120 new cases of non-Hodgkin lymphoma (NHL) in the USA in 2008. Radioimmunotherapy has been shown in clinical trials to be an effective treatment for refractory/relapsed NHL. The available agents are Bexxar, a (131)I radiolabeled murine monoclonal antibody, and Zevalin, a (90)Y radiolabeled murine antibody. Both target CD20 receptors present on the surface of lymphocytes. We present our clinical experience with Bexxar and Zevalin in the management of low-grade refractory or relapsed NHL.This is a retrospective study (Jan 2000-Jul 2006) of 67 patients with NHL, who were treated with Bexxar (31 patients, group A) or Zevalin (36 patients, group B) for refractory/relapsed disease. Group A included 16 men and 15 women, 35-81 years old (average, 59.3 +/- 13.4). Group B included 27 men and nine women, 36-85 years old (average, 55.4 +/- 13.8). Therapeutic doses ranged 40-138 mCi (average, 78.1 +/- 28.2) for Bexxar and 17-34 mCi (average, 28.8 +/- 4.37) for Zevalin.Objective responses were induced in 22 of the 31 patients (70.9%) in group A and 28 of the 36 patients (77.8%) in group B. Complete response was noted in 11 patients (35.5%), partial response in seven patients (22.6%), and mixed response in four patients (12.9%) in group A. There were five patients (16.1%) with stable disease and four patients (12.9%) with disease progression in the same group. Complete response was noted in 15 patients (41.7%), partial response in nine patients (25%), and mixed response in four patients (11.1%) in group B. There were four patients (11.1%) with stable disease and another four patients (11.1%) with disease progression in the same group. The average decreases at posttherapy nadir were 36.9% +/- 0.33 (group A) and 52.6% +/- 0.32 (group B) for platelets, 27.8% +/- 0.27 (group A) and 34.2% +/- 0.38 (group B) for leukocytes, and 4.9% +/- 0.15 (group A) and 7.6% +/- 0.11 (group B) for hemoglobin. Grades 3 and 4 hematological toxicity occurred in 14 patients (45.2%) treated with Bexxar and 22 patients (61.1%) treated with Zevalin, but was reversible.Our study suggests that clinical practice of Bexxar and Zevalin radioimmunotherapy is an effective and safe adjunctive treatment for patients with NHL refractory/relapsed to conventional treatment. However, due to the small number of subjects, it was not possible to determine whether differences in the outcomes or toxicities from the two agents were statistically significant.

  View details for DOI 10.1007/s11307-009-0245-9

  View details for Web of Science ID 000275974900010

  View details for PubMedID 19543946

• Combined F-18-FDG and Fluoride Approach in PET/CT Imaging: Is There a Clinical Future? REPLY JOURNAL OF NUCLEAR MEDICINE Iagaru, A., Mittra, E., Goris, M. L., Gambhir, S. S. 2010; 51 (1): 166-167

  View details for DOI 10.2967/jnumed.109.067082

  View details for Web of Science ID 000273263800030

• Efficacy of F-18-FDG PET/CT in the evaluation of patients with recurrent cervical carcinoma EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Mittra, E., El-Maghraby, T., Rodriguez, C. A., Quon, A., McDougall, I. R., Gambhir, S. S., Iagaru, A. 2009; 36 (12): 1952-1959

  Abstract

  Only a limited number of studies have evaluated the efficacy of 18F-FDG PET/CT for recurrent cervical carcinoma, which this study seeks to expand upon.This is a retrospective study of 30 women with cervical carcinoma who had a surveillance PET/CT after initial therapy. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated using a 2 × 2 contingency table with pathology results (76%) or clinical follow-up (24%) as the gold standard. The Wilson score method was used to perform 95% confidence interval estimations.The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for the detection of local recurrence at the primary site were 93, 93, 93, 86, and 96%, respectively. The same values for the detection of distant metastases were 96, 95, 95, 96, and 95%, respectively. Seventy-one percent of the scans performed in symptomatic patients showed true-positive findings. In comparison, 44% of scans performed in asymptomatic patients showed true-positive findings. But, all patients subsequently had a change in their management based on the PET/CT findings such that the effect was notable. The maximum standardized uptake value ranged from 5 to 28 (average: 13 ± 7) in the primary site and 3 to 23 (average: 8 ± 4) in metastases which were significantly different (p = 0.04).This study demonstrates favorable efficacy of 18F-FDG PET/CT for identification of residual/recurrent cervical cancer, as well as for localization of distant metastases.

  View details for DOI 10.1007/s00259-009-1206-x

  View details for Web of Science ID 000271979300004

  View details for PubMedID 19585114

• Role or FDG-PET/CT Surveillance for Patients with Classical Hodgkin's Disease in First Complete Response: The Stanford University Experience. 51st Annual Meeting and Exposition of the American-Society-of-Hematology Maeda, L. S., Horning, S. J., Iagaru, A. H., Lin, F. I., Hoppe, R. T., Rosenberg, S. A., Advani, R. H. AMER SOC HEMATOLOGY. 2009: 626–26

  View details for Web of Science ID 000272725801743

• Efficacy of F-18-FDG PET/CT for Breast Cancer Mittra, E., Quon, A., Gambhir, S. S., Iagaru, A. SPRINGER. 2009: S176–S176

  View details for Web of Science ID 000208690800091

• Survival after Y-90 radioembolization is predicted by dose distribution scintigraphy Sze, D. Y., Louie, J. D., Iagaru, A. H., Goris, M. L. SPRINGER. 2009: S279

  View details for Web of Science ID 000208690801093

• Prospective Evaluation of Tc-99m-MDP Scintigraphy, F-18 NaF PET/CT and F-18 FDG PET/CT for Detection of Skeletal Metastases Iagaru, A., Mittra, E., Dick, D., Gambhir, S. S. SPRINGER. 2009: S187–S187

  View details for Web of Science ID 000208690800141

• Evaluation by F-18-FDG-PET of patients with anal squamous cell carcinoma HELLENIC JOURNAL OF NUCLEAR MEDICINE Iagaru, A., Kundu, R., Jadvar, H., Nagle, D. 2009; 12 (1): 26-29

  Abstract

  Anal squamous cell carcinoma (ASCC) is a rare cancer of the gastrointestinal tract, representing less than 5% of the digestive malignancies. The cytological and/or histological confirmation of a suspected lesion should be followed by a complete imaging evaluation to determine the extent of disease. We are presenting our experience with (18)F-FDG PET in ASCC. This is a retrospective case series of patients diagnosed and treated for ASCC at our institution(s). A total of 14 (18)F-FDG PET scans (8 for initial staging, 6 for evaluation of response to chemotherapy and radiation therapy) were performed in 8 patients (6 men, 2 women). The patients were 33-60 years old (average: 44+/-9). Our results showed that PET demonstrated the primary lesion at initial evaluation in 7 of 8 anal cancers and showed FDG- avid lymph nodes in 4 patients. Metastatic nodal involvement was confirmed by pathology in 2 patients; in the other 2 patients pathology showed reactive follicular hyperplasia. In another patient, follow-up PET demonstrated progression of disease despite treatment, prompting a change in disease management. In the remaining 5 patients with follow-up PET, the scans confirmed interval resolution of the (18)F-FDG uptake in the primary lesion, suggesting good treatment response. In conclusion, PET provides valuable diagnostic information in initial staging and evaluation of treatment response in ASCC that may significantly alter the clinical management. The emergence of the combined PET/CT scanner enhanced the accuracy of the imaging procedure in view of the precise anatomic localization of metabolic abnormalities.

  View details for Web of Science ID 000265034600007

  View details for PubMedID 19330178

• Tumor Metabolic Phenotypes on F-18 FDG PET REPLY JOURNAL OF NUCLEAR MEDICINE Iagaru, A. H., Gambhir, S. S., Goris, M. L. 2009; 50 (6): 1011-1012

  View details for DOI 10.2967/jnumed.109.061945

  View details for Web of Science ID 000272488000034

• Phase II efficacy results using an oncolytic herpes simplex virus (NV1020) in patients with colorectal cancer metastatic to liver (mCRC) 45th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Geevarghese, S. K., Chen, A., Geller, D. A., de Haan, H. A., Iagaru, A., Knoll, A., Nemunaitis, J., Reid, T. R., Sze, D. Y., Tanabe, K. AMER SOC CLINICAL ONCOLOGY. 2009

  View details for Web of Science ID 000276606601031

• Incorporating Cone-beam CT into the Treatment Planning for Yttrium-90 Radioembolization JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Louie, J. D., Kothary, N., Kuo, W. T., Hwang, G. L., Hofmann, L. V., Goris, M. L., Iagaru, A. H., Sze, D. Y. 2009; 20 (5): 606-613

  Abstract

  To prepare for yttrium-90 ((90)Y) microsphere radioembolization therapy, digital subtraction angiography (DSA) and technetium- 99m-labeled macroaggregated albumin ((99m)Tc MAA) scintigraphy are used for treatment planning and detection of potential nontarget embolization. The present study was performed to determine if cone-beam computed tomography (CBCT) affects treatment planning as an adjunct to these conventional imaging modalities.From March 2007 to August 2008, 42 consecutive patients (21 men, 21 women; mean age, 59 years; range, 21-75 y) who underwent radioembolization were evaluated by CBCT in addition to DSA and (99m)Tc MAA scintigraphy during treatment planning, and their records were retrospectively reviewed. The contrast-enhanced territories shown by CBCT with selective intraarterial contrast agent administration were used to predict intrahepatic and possible extrahepatic distribution of microspheres.In 22 of 42 cases (52%), extrahepatic enhancement or incomplete tumor perfusion seen on CBCT affected the treatment plan. In 14 patients (33%), the findings were evident exclusively on CBCT and not detected by DSA. When comparing CBCT versus (99m)Tc MAA scintigraphy, CBCT showed eight cases of extrahepatic enhancement (19%) that were not evident on (99m)Tc MAA imaging. CBCT findings directed the additional embolization of vessels or repositioning of the catheter for better contrast agent and microsphere distribution. One case of gastric ulcer from nontarget embolization caused by reader error was observed.CBCT can provide additional information about tumor and tissue perfusion not currently detectable by DSA or (99m)Tc MAA imaging, which should optimize (90)Y microsphere delivery and reduce nontarget embolization.

  View details for DOI 10.1016/j.jvir.2009.01.021

  View details for PubMedID 19345589

• Phase II Efficacy Results Using an Oncolytic Herpes Simplex Virus (NV1020) in Patients with Colorectal Cancer Metastatic to Liver (mCRC) 12th Annual Meeting of the American Society of Gene Therapy Nemunaitis, J., Geevarghese, S. K., Geller, D. A., de Haan, H. A., Iagaru, A., Knoll, A., Reid, T. R., Sze, D. Y., Tanabe, K. NATURE PUBLISHING GROUP. 2009: S304–S304

  View details for Web of Science ID 000278019801365

• Novel Strategy for a Cocktail F-18-Fluoride and F-18-FDG PET/CT Scan for Evaluation of Malignancy: Results of the Pilot-Phase Study JOURNAL OF NUCLEAR MEDICINE Iagaru, A., Mittra, E., Yaghoubi, S. S., Dick, D. W., Quon, A., Goris, M. L., Gambhir, S. S. 2009; 50 (4): 501-505

  Abstract

  (18)F-FDG PET/CT is used for detecting cancer and monitoring cancer response to therapy. However, because of the variable rates of glucose metabolism, not all cancers are identified reliably. Sodium (18)F was previously used for bone imaging and can be used as a PET/CT skeletal tracer. The combined administration of (18)F and (18)F-FDG in a single PET/CT study for cancer detection has not been reported to date.This is a prospective pilot study (November 2007-November 2008) of 14 patients with proven malignancy (6 sarcoma, 3 prostate cancer, 2 breast cancer, 1 colon cancer, 1 lung cancer, and 1 malignant paraganglioma) who underwent separate (18)F PET/CT and (18)F-FDG PET/CT and combined (18)F/(18)F-FDG PET/CT scans for the evaluation of malignancy (a total of 3 scans each). There were 11 men and 3 women (age range, 19-75 y; average, 50.4 y).Interpretation of the combined (18)F/(18)F-FDG PET/CT scans compared favorably with that of the (18)F-FDG PET/CT (no lesions missed) and the (18)F PET/CT scans (only 1 skull lesion seen on an (18)F PET/CT scan was missed on the corresponding combined scan). Through image processing, the combined (18)F/(18)F-FDG scan yielded results for bone radiotracer uptake comparable to those of the (18)F PET/CT scan performed separately.Our pilot-phase prospective trial demonstrates that the combined (18)F/(18)F-FDG administration followed by a single PET/CT scan is feasible for cancer detection. This combined method opens the possibility for improved patient care and reduction in health care costs.

  View details for DOI 10.2967/jnumed.108.058339

  View details for Web of Science ID 000272487200003

  View details for PubMedID 19289439

• F-18-FDG PET/CT evaluation of patients with ovarian carcinoma NUCLEAR MEDICINE COMMUNICATIONS Iagaru, A. H., Mittra, E. S., McDougall, I. R., Quon, A., Gambhir, S. S. 2008; 29 (12): 1046-1051

  Abstract

  The role of F-FDG PET has been studied in ovarian carcinoma, but its sensitivity and specificity calculations are based on dedicated PET acquisition, not PET/CT in the majority of the published studies. Therefore, we were prompted to review our experience with PET/CT in the management of patients with ovarian carcinoma.This is a retrospective study of 43 women with ovarian carcinoma, 27-80 years old (average: 53.9+/-7.8), who had whole-body PET/CT at our institution from 1 January 2003 to 31 August 2006. We reviewed the patients' outcomes from medical records and compared them to the interpretation of the PET/CT scans. Sensitivity and specificity were calculated using a 2 x 2 table with pathology results (79.1% of the patients) or clinical follow-up (20.9% of the cases) as the 'gold standard'. Confidence interval (CI) estimations were performed using the Wilson score method.All patients had advanced stage ovarian cancer and the study was requested for re-staging. A total of 60 scans were performed: 30 patients had one scan, nine patients had two scans and four patients had three scans. The administered doses of F-FDG ranged from 381.1 to 769.6 MBq (average: 569.8+/-73.3). PET/CT had a sensitivity of 88.4% (95% CI: 75.1-95.4) and a specificity of 88.2% (95% CI: 64.4-97.9) for detection of ovarian cancer. The SUV max of the detected lesions ranged from 3 to 27 (average: 9.4+/-5.9). The CA-125 tumor marker ranged from 3 to 935 kU/ml (average: 265.2) in patients with positive scans and 4-139 kU/ml (average: 17.1) in patients with negative scans. This difference was statistically significant (P value: 0.0242).This study confirms the good results of F-FDG PET/CT for identification of residual/recurrent ovarian cancer, as well as for distant metastases localization. PET/CT should be an integral part in evaluation of patients with high-risk ovarian cancer or rising values of tumor markers (CA-125), prior to selection of the most appropriate therapy.

  View details for DOI 10.1097/MNM.0b013e32831089cb

  View details for Web of Science ID 000261164200004

  View details for PubMedID 18987524

  View details for PubMedCentralID PMC2651960

• Y-90-Ibritumomab Therapy in Refractory Non-Hodgkin's Lymphoma: Observations from In-111-Ibritumomab Pretreatment Imaging JOURNAL OF NUCLEAR MEDICINE Iagaru, A., Gambhir, S. S., Goris, M. L. 2008; 49 (11): 1809-1812

  Abstract

  Radioimmunotherapy is an effective treatment for non-Hodgkin's lymphoma (NHL). 90Y-ibritumomab is an antibody targeting CD20 receptors on the surface of lymphocytes. We present observations from our clinical experience with 90Y-ibritumomab in the management of NHL.This was a retrospective study of 28 NHL patients treated with 90Y-ibritumomab. There were 21 men and 7 women, 36-85 y old. A diagnostic dose of 111In-ibritumomab was administered on day 0, and imaging followed immediately and at 24, 48, and 72 h. The doses of 90Y-ibritumomab ranged from 629 to 1,258 MBq (17-34 mCi). Outcomes were compared with the findings of the 111In-ibritumomab scans.90Y-ibritumomab induced objective responses in 22 of 28 patients. A complete response was noted in 9 patients, a partial response in 9 patients, and a mixed response in 4 patients. Three patients had stable disease, and 3 patients had disease progression. 111In-ibritumomab findings were positive in 19 patients and negative in 9 patients. A complete response was noted in 2 of 19 patients with positive findings and 7 of 9 with negative findings. A partial response was seen in 7 of 19 patients with positive findings and 1 of 9 with negative findings. Disease progression was observed in 3 of 19 patients with positive findings and 0 of 9 with negative findings. The remaining patients had a mixed response or no changes.A higher rate of complete response after 90Y-ibritumomab treatment was seen in patients with negative 111In-ibritumomab findings, whereas a higher rate of disease progression despite therapy was noted in patients with positive 111In-ibritumomab findings. This observation suggests that patients with bulky disease may require more aggressive management.

  View details for DOI 10.2967/jnumed.108.052928

  View details for Web of Science ID 000260846600019

  View details for PubMedID 18927323

• I-131-Tositumomab (Bexxar (R)) Therapy of Refractory/Relapsed Non-Hodgkin Lymphoma: Clinical Experience Iagaru, A., Knox, S., Goris, M. L. SPRINGER. 2008: S148–S149

  View details for Web of Science ID 000208690700101

• F-18 FDG PET/CT Evaluation of Osseous and Soft Tissue Sarcomas: Differences between Adult and Pediatric Patients Iagaru, A., Mittra, E., Quon, A., Jacobs, C., Marina, N., Gambhir, S. S. SPRINGER. 2008: S155

  View details for Web of Science ID 000208690700129

• Rhabdomyosarcoma diffusely metastatic to the bone marrow: suspicious findings on Tc-99m-MDP bone scintigraphy confirmed by F-18-18 FDG PET/CT and bone marrow biopsy EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Iagaru, A., Goris, M. L. 2008; 35 (9): 1746-1746

  View details for DOI 10.1007/s00259-008-0864-4

  View details for Web of Science ID 000258673800026

  View details for PubMedID 18648808

• F-18-FDG-PET/CT evaluation of response to treatment in lymphoma: when is the optimal time for the first re-evaluation scan? HELLENIC JOURNAL OF NUCLEAR MEDICINE Iagaru, A., Wang, Y., Mari, C., Quon, A., Goris, M. L., Horning, S., Gambhir, S. S. 2008; 11 (3): 153-156

  Abstract

  Assessing the response to treatment as soon after treatment initiation is one of the key reasons for imaging lymphoma patients. The optimal time after initiating treatment for assessing response to treatment has yet to be determined. Therefore, we were prompted to review our experience with serial (18)F-FDG PET/CT in patients undergoing treatment for Hodgkin's disease (HD) and non Hodgkin's lymphoma (NHL). This is a retrospective study (Feb 2003 - Oct 2004) of 20 patients, 11 men and 9 women, with age range of 7-75 years with diagnosis of HD (10) and NHL (10), who had PET/CT at our institution prior, during and at the completion of therapy. Restaging PET/CT was done after 2 cycles of chemotherapy in 10 patients (group A) and after 4 cycles of chemotherapy in 10 pts (group B). A total of 60 scans were reviewed. The DeltaSUV from baseline to first PET/CT was on average 67.6% in group A and 75.1% in group B. This had no statistical significance (P value: 0.31). The DeltaSUV from baseline to post-therapy PET/CT was on average 72.9% in group A and 79.8% in group B. This difference also had no statistical significance (P value: 0.24). The correlation coefficient was 0.98 in group A and 0.80 in group B. Results of PET/CT after 2 cycles of chemotherapy did not statistically differ from the results of PET/CT after 4 cycles of chemotherapy. These results need to be confirmed in larger, prospective, randomized trials.

  View details for Web of Science ID 000262093600003

  View details for PubMedID 19081857

• Imaging characteristics and response after intraarterial administration of the oncolytic herpes virus NV1020 to treat hepatic colorectal metastases Sze, D. Y., Gambhir, S. S., Chari, R. S., Geller, D. A., Iagaru, A., Mescheder, A., Nemunaitis, J. J., Reid, T. R., Tanabe, K. AMER SOC CLINICAL ONCOLOGY. 2008

  View details for Web of Science ID 000208457401384

• Perspectives of molecular imaging and radioimmunotherapy in lymphoma RADIOLOGIC CLINICS OF NORTH AMERICA Iagaru, A., Goris, M. L., Gambhir, S. S. 2008; 46 (2): 243-252

  Abstract

  Successful treatment of Hodgkin lymphomas and non-Hodgkin lymphomas depends on accurate staging and prognostic estimations, as well as evaluation of response to therapy as early after initiation as possible. We focus on several aspects of molecular imaging and therapy that affect the management of patients who have lymphoma. First, we review prior use of gallium-67 citrate for evaluation of lymphoma patients, mainly from a historical perspective, since it was the mainstream lymphoma functional imaging tracer for decades. Next, we review current clinical uses of 18F Fluoro-2-Deoxyglucose (18F FDG) PET and PET/CT for evaluation of lymphoma patients and use of radioimmunotherapy in lymphoma. Finally, we discuss advances in molecular imaging that may herald the next generation of PET radiotracers after 18F FDG.

  View details for DOI 10.1016/j.rcl.2008.03.007

  View details for Web of Science ID 000258543500006

  View details for PubMedID 18619379

• I-123 MIBG mapping with intraoperative gamma probe for recurrent neuroblastoma MOLECULAR IMAGING AND BIOLOGY Iagaru, A., Peterson, D., Quon, A., Dutta, S., Twist, C., Daghighian, F., Gambhir, S. S., Albanese, C. 2008; 10 (1): 19-23

  Abstract

  Intraoperative gamma probe guidance has become widely utilized for sentinel lymph node dissection in patients with breast cancer and melanoma, using (99m)Tc sulfur colloid. However, new indications are possible and need to continue to be investigated. We report the use during a wedge liver biopsy of a new hand-held gamma probe designed for (123)I intraoperative guidance. The patient studied is a 5-year-old boy with history of stage 4 high-risk neuroblastoma. Anatomic imaging (CT, MRI), (99m)Tc bone scintigraphy and 2-deoxy-2-[F-18]fluoro-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) were negative, but the (123)I MIBG scintigraphy suggested recurrent liver disease. A decision was made to biopsy these lesions to obtain histopathological confirmation. Intraoperative gamma probe mapping of the liver identified areas with signal above the background, but these were prove to be hemosiderin deposits on histo-pathology examination.

  View details for DOI 10.1007/s11307-007-0116-1

  View details for Web of Science ID 000252107800002

  View details for PubMedID 17975716

• F-18FDG PET and PET/CT evaluation of response to chemotherapy in bone and soft tissue sarcomas CLINICAL NUCLEAR MEDICINE Iagaru, A., Masamed, R., Chawla, S. P., Menendez, L. R., Fedenko, A., Conti, P. S. 2008; 33 (1): 8-13

  Abstract

  F-18 FDG PET has been used to grade sarcomas and assess response to therapy in advanced disease. Certain chemotherapy agents are thought to induce an inflammatory response in the tumor bed that can make interpretation of post-therapy FDG PET scans difficult. A review of our experience with PET in assessing therapy response in osseous and soft tissue sarcomas (OSTS) is presented.This is a retrospective study (January 1999 to December 2004) of 14 patients with histologic diagnosis of OSTS, who had 2 consecutive PET examinations for evaluation of chemotherapy response. The group included 8 men and 6 women, with age range of 18 to 56 years (average, 36 +/- 14). Semiquantitative assessment of FDG uptake was performed by calculating maximum standard uptake value (SUVmax) before and after treatment. The response to therapy was assessed independently by tumor necrosis at post-therapy surgery and according to European Organization for Research and Treatment of Cancer (EORTC) criteria for PET. The follow-up PET examinations were performed at an interval of 28 to 166 days (average, 90 +/- 45). All patients ended the ifosfamide regimen at 7 to 36 (average, 16 +/- 9) days before the follow-up PET scans. Five of them received methotrexate, adriamycin, and/or cisplatin as well.Based on the EORTC criteria alone, 3 patients (21.4%) had progression of disease (increase in SUVmax of 29%-69%; mean, 48% +/- 20%), 5 patients (35.7%) had stable disease, and 6 patients (42.8%) had partial response (decrease in SUVmax of 27%-84%; mean, 62% +/- 23%). Across all patients, the tumor necrosis postchemotherapy ranged from 5% to 100% (mean, 64% +/- 34%). In 8 patients (57.1%) the tumor necrosis correlated with the SUVmax changes. However, for 3 patients, the SUVmax changes indicated partial response despite necrosis of fewer than 90% of the surgical specimens, whereas 3 patients with >90% tumor necrosis had SUVmax changes indicative of stable disease.The pathologically determined degree of necrosis postneoadjuvant chemotherapy was concordant with PET-assessed EORTC classification of response in 57.1% of the cases. However, a significant number of patients had discrepancies, which may be in part explained by chemotherapy-induced inflammation. The latter should be considered during post-therapy PET interpretation in OSTS.

  View details for Web of Science ID 000252074200003

  View details for PubMedID 18097248

• Molecular imaging can accelerate anti-angiogenic drug development and testing NATURE CLINICAL PRACTICE ONCOLOGY Lagaru, A., Chen, X., Gambhir, S. S. 2007; 4 (10): 556-557

  View details for DOI 10.1038/ncponc0929

  View details for Web of Science ID 000249708800002

  View details for PubMedID 17726490

• PET Imaging of Skull Base Neoplasms. PET clinics Mittra, E. S., Iagaru, A., Quon, A., Fischbein, N. 2007; 2 (4): 489-510

  Abstract

  The utility of 18-F-fluorodeoxyglucose-positron emission tomography (PET) and PET/CT for the evaluation of skull base tumors is incompletely investigated, as a limited number of studies specifically focus on this region with regard to PET imaging. Several patterns can be ascertained, however, by synthesizing the data from various published reports and cases of primary skull base malignancies, as well as head and neck malignancies that extend secondarily to the skull base, including nasopharyngeal carcinoma, nasal cavity and paranasal sinus tumors, parotid cancers, and orbital tumors.

  View details for DOI 10.1016/j.cpet.2008.05.006

  View details for PubMedID 27158109

• Osseous and soft tissue sarcomas: When can F-18 FDG PET/CT evaluation provide useful information? 20th Annual Congress of the European-Association-of-Nuclear-Medicine Iagaru, A., Quon, A., Jacobs, C., Marina, N., McDougall, I., Gambhir, S. S. SPRINGER. 2007: S152–S152

  View details for Web of Science ID 000253283900155

• F-18 FDG PET/CT in the management of thyroid cancer CLINICAL NUCLEAR MEDICINE Iagaru, A., Kalinyak, J. E., McDougall, I. R. 2007; 32 (9): 690-695

  Abstract

  There are approximately 32,000 new cases of thyroid carcinoma annually in the United States. F-18 FDG PET/CT has an established role in cancer management, including thyroid cancer, usually in patients who are thyroglobulin (Tg) positive/iodine negative. We reviewed our experience with F-18 FDG PET/CT in thyroid cancer, with an emphasis on correlation with Tg, and maximum standardized uptake values (SUV). We also analyzed the role of thyroid stimulating hormone (TSH) on PET/CT results.This is a retrospective study (January 2003 to December 2006) of 76 patients with differentiated thyroid cancer, who had F-18 FDG PET/CT scans. There were 44 women and 32 men, with age range of 20 to 81 years (average, 51.1 +/- 18.1). The administered doses of F-18 FDG ranged from 396 to 717 MBq (15.8-19.4 mCi) (average, 566 +/- 74.8) (15.3 +/- 2). Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed.A total of 98 PET/CT scans were analyzed (59 patients had 1 scan, 12 patients had 2, and 5 patients had 3). PET/CT was 88.6% sensitive (95% CI: 78.-94.3) and 89.3% specific (95% CI: 71.9-97.1). Mean Tg level was 1203 ng/mL (range, 0.5-28,357) in patients with positive PET/CT and 9.72 ng/mL (range, 0.5-123.0) in patients with negative PET/CT scans (P = 0.0389). Mean SUV max was 10.8 (range, 2.5-32) in the thyroid bed recurrence/residual disease and 7.53 (range, 2.5-26.2) in metastatic lesions (P = 0.0114). Mean SUV max in recurrent/residual disease in patients with TSH 30 mIU/L was 8.1 (range, 2.6-32) (P = 0.2994).F-18 FDG PET/CT had excellent sensitivity (88.6%) and specificity (89.3%) in this patient population. Metastatic lesions were reliably identified, but were less F-18 FDG avid than recurrence/residual disease in the thyroid bed. TSH levels at the time of PET/CT did not appear to impact the FDG uptake in the lesions or the ability to detect disease. In the setting of high or rising levels of Tg, our study confirms that it is indicated to include PET/CT in the management of patients with differentiated thyroid cancer.

  View details for Web of Science ID 000248959000004

  View details for PubMedID 17710020

• Antithyroid drugs and radioiodine and the absence of evidence - Reply JOURNAL OF NUCLEAR MEDICINE McDougall, I. R., Iagaru, A. 2007; 48 (8): 1403-1404

  View details for DOI 10.2967/jnumed.107.041897

  View details for Web of Science ID 000248584300042

• Advances in metabolic imaging for surgical oncology SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA Iagaru, A., Quon, A. 2007; 16 (2): 273-?

  Abstract

  This review focuses on several aspects of molecular imaging. First, current positron emission tomography (PET)/CT scanner technology and several novel imaging techniques that are being developed are briefly discussed. Next, current clinical indications for (18)F FDG PET and PET/CT that are relevant to the surgical oncologist are discussed. Finally, advances in molecular imaging that may herald the next generation of PET radiotracers beyond (18)F FDG are reviewed.

  View details for DOI 10.1016/j.soc.2007.03.007

  View details for Web of Science ID 000247901000003

  View details for PubMedID 17560512

• Detection of occult medullary thyroid cancer recurrence with 2-deoxy-2-[F-18]fluoro-D-glucose-PET and PET/CT MOLECULAR IMAGING AND BIOLOGY Iagaru, A., Masamed, R., Singer, P. A., Conti, P. S. 2007; 9 (2): 72-77

  Abstract

  2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET) has an established role in restaging of various cancers, including papillary and undifferentiated thyroid carcinoma. However, controversies exist regarding its ability to reliably assess recurrent medullary thyroid cancer (MTC). We were therefore prompted to review our experience with FDG-PET for detection of occult MTC.This is a retrospective study (Apr 1, 1997-Mar 31, 2004) of 13 patients with histologic diagnosis of MTC, who had PET examinations. The group included six men and seven women, 15-62 years old (average: 48+/-13). The PET scan request was triggered by rising levels of calcitonin and negative anatomical imaging studies.Recurrent/metastatic disease was identified by PET in seven (54%) of the 13 patients. The lesions were located in superior mediastinum (4), cervical lymph nodes (3), thyroid bed (2), lung (1) and liver (1). The calcitonin levels ranged from 52 to 5,090 pg/ml (average: 1,996 pg/ml) in patients with negative PET scans and from 132 to 9,500 pg/ml (average: 3,757 pg/ml) in patients with positive studies. The sensitivity and specificity of FDG-PET for disease detection in this cohort were 85.7% (95% CI: 48.7-97.4) and 83.3% (95% CI: 43.6-96.9), respectively.Our findings suggest a significant role for FDG-PET in patients with suspected MTC recurrence, with sensitivity of 85.7% and specificity of 83.3% for disease detection. FDG-PET provides additional information in a significant fraction of cases (54%) and could be used for restaging of patients with MTC and elevated levels of biomarkers (calcitonin). Additional studies are necessary to further evaluate the role of FDG-PET in MTC.

  View details for DOI 10.1007/s11307-006-0072-1

  View details for Web of Science ID 000244866700003

  View details for PubMedID 17186139

• Treatment of thyrotoxicosis JOURNAL OF NUCLEAR MEDICINE Iagaru, A., McDougall, I. R. 2007; 48 (3): 379-389

  Abstract

  In this review, the causes of thyrotoxicosis and the treatment of syndromes with increased trapping of iodine are discussed. The benefits and the potential side effects of 3 frequently used therapies--antithyroid medications, thyroidectomy, and (131)I treatment--are presented. The different approaches to application of (131)I treatment are described. Treatment with (131)I has been found to be cost-effective, safe, and reliable.

  View details for Web of Science ID 000244937400016

  View details for PubMedID 17332615

• F-18 FDG PET visualization of urinary leak after nephrostomy tube removal CLINICAL NUCLEAR MEDICINE Iagaru, A., Gamie, S., Segall, G. 2007; 32 (2): 168-169

  View details for PubMedID 17242582

• Follicular dendritic sarcoma within a focus of Castleman's disease. Serial FDG PET/CT in the follow up of recurrence with histopathologic confirmation REVISTA ESPANOLA DE MEDICINA NUCLEAR Iagaru, A., Mari, C., Gambhir, S. S. 2007; 26 (1): 40-45

  Abstract

  We report the case of a 30 year-old man with previous history of melanoma and new diagnoses of localized abdominal Castleman's disease with a focus of follicular dendritic sarcoma within the Castleman's tumor. He presented soon after with a single enlarged abdominal lymph node characterized and followed-up by FDG PET/CT as a low grade malignancy consistent with Castleman's recurrence. However, other imaging techniques raised the possibility of sarcoma/ melanoma recurrence. Final surgical resection allowed histological confirmation of the FDG PET/CT findings. To our knowledge, this is one of the few cases in the literature of Castleman's disease and follicular dendritic sarcoma association in the same focus. This is the first paper to our knowledge to use FDG PET/CT as the follow-up imaging tool for serial characterization of recurrence of Castleman's disease and follicular dendritic sarcoma. FDG PET/CT may be useful in the differentiation between Castleman's disease and malignancies associated with this disease.

  View details for Web of Science ID 000254133000006

  View details for PubMedID 17286947

• 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography/computed tomography in the management of melanoma MOLECULAR IMAGING AND BIOLOGY Iagaru, A., Quon, A., Johnson, D., Gambhir, S. S., McDougall, I. R. 2007; 9 (1): 50-57

  Abstract

  2-Deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is widely available as a powerful imaging modality, combining the ability to detect active metabolic processes and their morphologic features in a single exam. The role of FDG-PET is proven in a variety of cancers, including melanoma, but the estimates of sensitivity and specificity are based in the majority of the published studies on dedicated PET, not PET/CT. Therefore, we were prompted to review our experience with FDG-PET/CT in the management of melanoma.This is a retrospective study on 106 patients with melanoma (20-87 years old; average: 56.8 +/- 15.9), who had whole-body FDG-PET/CT at our institution from January 2003 to June 2005. Thirty-eight patients (35.9%) were women and 68 patients (64.1%) were men. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed.All patients had the study for disease restaging. The primary tumor depth (Breslow's thickness) at initial diagnosis was available for 76 patients (71.7%) and ranged from 0.4 to 25 mm (average: 3.56 mm). The anatomic level of invasion in the skin (Clark's level) was determined for 70 patients (66%): 3, level II; 13, level III; 43, level IV; 11, level V. The administered dose of (18)F FDG ranged from 9.8 to 21.6 mCi (average: 15.4 +/- 1.8 mCi). FDG-PET/CT had a sensitivity of 89.3% [95% confidence interval (CI): 78.5-95] and a specificity of 88% (95% CI: 76.2-94.4) for melanoma detection.This study confirms the good results of FDG-PET/CT for residual/recurrent melanoma detection, as well as for distant metastases localization. PET/CT should be an integral part in evaluation of patients with high-risk melanoma, prior to selection of the most appropriate therapy.

  View details for DOI 10.1007/s11307-006-0065-0

  View details for Web of Science ID 000243545600007

  View details for PubMedID 17051322

• F-18FDG PET/CT demonstration of an adrenal metastasis in a patient with anaplastic thyroid cancer CLINICAL NUCLEAR MEDICINE Iagaru, A., McDougall, I. R. 2007; 32 (1): 13-15

  Abstract

  An adrenal metastasis was identified on an F-18 FDG PET/CT scan in a patient with anaplastic thyroid cancer. There are very few reports of thyroid cancer, even anaplastic thyroid cancer, metastasizing to the adrenal.

  View details for Web of Science ID 000243200800004

  View details for PubMedID 17179796

• Breast MRI and F-18 FDG PET/CT in the management of breast cancer ANNALS OF NUCLEAR MEDICINE Iagaru, A., Masamed, R., Keesara, S., Conti, P. S. 2007; 21 (1): 33-38

  Abstract

  18F FDG PET/CT is used for diagnosis, staging and establishing the response to therapy in various malignancies, including breast cancer (BC). Dedicated breast MRI (BMRI) is gaining a role in the management of BC patients (pts), demonstrating high sensitivity and specificity for detection of small lesions. We were therefore prompted to review our experience with PET and BMRI in BC.This is a retrospective study of 21 women with BC, 30-76 years old, who had BMRI and whole-body FDG PET/CT at our institution from Jun 2002 to May 2005. A total of 6 patients (group A) had BMRI and PET/CT in the preoperative period and 15 patients (group B) had BMRI and PET/CT after surgery. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed.For group A, BMRI identified breast lesions in 4 patients, while PET/CT was able to identify breast lesions in 5 patients. All these were proven to be malignancy on pathology examination. In group B, BMRI detected recurrent breast lesions in 8 patients, with 88.9% sensitivity and 83.3% specificity. In the same patient population, PET/CT was 33.3% sensitive and 91.7% specific. As a whole body examination, PET/CT revealed metastatic disease in 6 patients (100% sensitive and 90% specific). Overall, sensitivities and specificities for breast disease detection were 85.7% and 85.7% for BMRI, and 75% and 92.3% for 18F FDG PET/ CT.As expected, BMRI is more sensitive than PET/CT in the detection of breast lesions. However, PET/CT as a whole-body examination changed the management of disease by detection of distant lesions in 6 of the 21 patients. Our study suggests that 18F FDG PET/CT and BMRI should be considered as complimentary imaging tools in the pre- and postoperative work-up of patients diagnosed with breast cancer.

  View details for Web of Science ID 000244431300005

  View details for PubMedID 17373334

• F-18FDG PET/CT evaluation of osseous and soft tissue sarcomas CLINICAL NUCLEAR MEDICINE Iagaru, A., Quon, A., McDougall, T. R., Gambhir, S. S. 2006; 31 (12): 754-760

  Abstract

  Osseous and soft tissue sarcomas (OSTS) represent a histologic heterogeneous group of malignant tumors. Most of the current clinical data on the role of F-18 FDG PET in sarcomas come from patients studied with dedicated PET and less frequently with hardware fusion PET/CT. Therefore, we were prompted to review our experience with F-18 FDG PET/CT in OSTS.This is a retrospective study (January 2003-December 2005) of 44 patients with histologic diagnoses of OSTS who had F-18 FDG PET/CT at our institution. The group included 22 men and 22 women with an age range of 2 of 84 years (average, 37 +/- 20.2 years). The administered doses of F-18 FDG range 4.1 to 19.5 mCi (average, 14.3 +/- 3 mCi). Reinterpretation of the imaging studies for accuracy and data analysis from medical records was performed.The sensitivity and specificity of combined F-18 FDG PET/CT were 100% (95% confidence interval [CI] = 75.7-100) and 93.3% (95% CI = 78.7-98.1) for the primary OSTS, and 80% (95% CI = 58.4-91.9) and 86.4% (95% CI = 66.7-95.2) for metastases. When interpreted separately, CT outperformed PET for pulmonary metastases detection: CT was 76.5% sensitive and 88% specific, whereas PET was only 57.1% sensitive but 96.4% specific. For detection of other metastases, CT was 82.3% sensitive and 76% specific, with PET demonstrating 78.6% sensitivity and 92.8% specificity.Relatively similar results (except better specificity for PET and PET/CT) were noted when examining the rate of metastases detection, excluding pulmonary lesions. However, CT had a better detection rate for pulmonary metastases when compared with PET alone. A negative PET scan in the presence of suspicious CT findings in the chest cannot reliably exclude pulmonary metastases from OSTS.

  View details for Web of Science ID 000242481400004

  View details for PubMedID 17117068

• F-18-FDG PET and PET/CT for detection of pulmonary metastases from musculoskeletal sarcomas NUCLEAR MEDICINE COMMUNICATIONS Iagaru, A., Chawla, S., Menendez, L., Conti, P. S. 2006; 27 (10): 795-802

  Abstract

  Sarcomas represent a significant therapeutic challenge and their potential for distant pulmonary metastases is well known. [(18)F]Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) has a role in differentiating sarcomas from benign tumours and assessing the response to therapy in advanced sarcomas. However, PET appears to be less accurate in detection of pulmonary metastases. We were therefore prompted to review our experience with PET and PET/computed tomography (CT) in osseous and soft tissue sarcomas (OSTSs).This is a retrospective study (January 1995 to December 2004) of 106 patients with histological diagnosis of OSTS, who had PET and PET/CT at our institution. The group included 52 men and 54 women, aged 12-92 years (average, 45+/-20 years).For all the patients in the analysis, the sensitivity and specificity were 68.3% (95% CI: 53-80.4) and 98.4% (95% CI: 91.8-99.7) for PET, with 95.1% sensitivity (95% CI: 83.8-98.6) and 92.3% specificity (95% CI: 83.2-96.7) for CT. Pulmonary metastases were seen in 40 patients. CT identified 17 lesions larger than 1.0 cm, while PET identified 13 of them (76.5%).Chest CT is more sensitive than PET in detecting pulmonary metastases from OSTS. A significant portion of known pulmonary metastases greater than 1.0 cm on CT, are PET negative. Sub-centimetre CT lesions should not be considered false positive if inactive on PET. A negative PET scan in the presence of suspicious CT findings in the chest cannot reliably exclude pulmonary metastases from OSTS.

  View details for Web of Science ID 000241089000008

  View details for PubMedID 16969262

• 2-Deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography and positron emission tomography/computed tomography diagnosis of patients with recurrent papillary thyroid cancer MOLECULAR IMAGING AND BIOLOGY Iagaru, A., Masamed, R., Singer, P. A., Conti, P. S. 2006; 8 (5): 309-314

  Abstract

  2-Deoxy-2-[F-18]fluoro-D-glucose positron emission tomography (FDG-PET) has an established role in restaging of various cancers, including papillary and undifferentiated thyroid carcinoma, but detection rates are variable in the published literature. We were therefore prompted to review our experience with FDG-PET in detection of recurrent papillary thyroid cancer (PTC).This is a retrospective study (April 1, 1995-March 31, 2005) of 21 patients with histologic diagnosis of PTC who had PET examinations. The group included seven men and 14 women, with age range of 26-75 years (average 50 +/- 16). The PET scan request was triggered by rising levels of thyroglobulin (Tg) in the presence of a negative iodine-131 scan.Recurrent/metastatic disease was identified by PET in 16 (76%) of the 21 patients with PTC. The sensitivity and specificity of FDG-PET for disease detection in this cohort were 88.2% [95% confidence interval (CI), 65.7-96.7] and 75% (95% CI, 30.1-95.4), respectively. The Tg levels were 1.0-10.4 ng/ml (average, 4.52 ng/ml) in the patients with negative PET scans and 1.0-38 ng/ml (average, 16.8 ng/ml) in patients with positive scans. The lesions were located in the cervical lymph nodes (8), thyroid bed (4), lungs (4), and mediastinal lymph nodes (2).Our study confirms the feasibility of PET in detection of residual/recurrence of PTC, with sensitivity of 88.2% (95% CI, 65.7-96.7) and specificity of 75% (95% CI, 30.1-95.4). Detectable levels of Tg, even in the presence of negative I-131 scan or anatomic imaging, should prompt restaging with FDG-PET.

  View details for DOI 10.1007/s11307-006-0046-3

  View details for Web of Science ID 000240560800008

  View details for PubMedID 16758370

• Demonstration of an ectopic mediastinal parathyroid adenoma on Tc-99m sestamibi myocardial perfusion scintigraphy JOURNAL OF NUCLEAR CARDIOLOGY Iagaru, A., Hachamovitch, R., Colletti, P. M., Wassef, H. 2006; 13 (5): 719-721

  View details for DOI 10.1016/j.nuclcard.2006.06.125

  View details for Web of Science ID 000240320900017

  View details for PubMedID 16945752

• PET/CT follow-up in nonossifying fibroma AMERICAN JOURNAL OF ROENTGENOLOGY Iagaru, A., Henderson, R. 2006; 187 (3): 830-832

  View details for DOI 10.2214/AJR.05.0264

  View details for Web of Science ID 000240259300040

  View details for PubMedID 16928954

• F-18FDG PET imaging of urinary bladder oat cell carcinoma with widespread osseous metastases CLINICAL NUCLEAR MEDICINE Iagaru, A., Gamie, S., Segall, G. 2006; 31 (8): 476-478

  View details for PubMedID 16855436

• Merkel cell carcinoma: Is there a role for 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography/computed tomography? MOLECULAR IMAGING AND BIOLOGY Iagaru, A., Quon, A., McDougall, I. R., Gambhir, S. S. 2006; 8 (4): 212-217

  Abstract

  2-Deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is becoming widely available as a powerful imaging modality, combining the ability to detect active metabolic processes and their morphologic features in a single study. The role of FDG-PET/CT is proven in lymphoma, melanoma, colorectal carcinoma, and other cancers. However, there are rare malignancies such as Merkel cell carcinoma that can potentially be evaluated with PET/CT. We were therefore prompted to review our experience with FDG-PET/CT in the management of patients with Merkel cell carcinoma.This is a retrospective case series of six patients with Merkel cell carcinoma, 58-81 years old (average 69 +/- 8.3), who had whole-body PET/CT at our institution from January 1st, 2003 to August 31st, 2005. Two patients were women and four were men. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed.Twelve examinations were acquired for the six patients (one patient had six PET/CT, one patient had two PET/CT, and four patients had one PET/CT). The injected FDG doses ranged 381.1-669.7 MBq (average 573.5 +/- 70.3). Four patients had the PET/CT as part of initial staging, and two patients had the exam for restaging (after surgery and XRT). A total of six Merkel lesions (pancreas, adrenal, lip, submandibular lymph nodes, cervical lymph nodes, and parapharyngeal soft tissue) were identified in three patients and confirmed on histopathological examination. The FDG uptake in these areas was intense, with maximum standardized uptake value (SUVmax) values of 5-14 (average 10.4 +/- 3.8). In one patient, the PET/CT scan identified abnormal focal distal sigmoid uptake that was biopsied and diagnosed as adenocarcinoma. Two patients had negative scans and had no clinical evidence of disease on follow-up office visits (up to one year after PET/CT).This case series suggests that FDG-PET/CT may have a promising role in the management of patients with Merkel cell carcinoma.

  View details for DOI 10.1007/s11307-006-0047-2

  View details for Web of Science ID 000239124800003

  View details for PubMedID 16724293

• F-18FDG PET evaluation of bronchial plasmacytoma with CT and MRI correlation CLINICAL NUCLEAR MEDICINE Iagaru, A., Mari, C., Segall, G. 2006; 31 (5): 279-280

  View details for PubMedID 16622337

• Demonstration of a right inguinal hernia containing urinary bladder diverticulum on whole-body bone scan and pelvic CT EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Iagaru, A., Siegel, M. E. 2006; 33 (2): 234-234

  View details for DOI 10.1007/s00259-005-1977-7

  View details for Web of Science ID 000234934800021

  View details for PubMedID 16344994

• Failed atrial septal defect repair versus pulmonary hypertension with right ventricular failure CLINICAL NUCLEAR MEDICINE Iagaru, A., Wassef, H., Henderson, R. 2005; 30 (11): 767-768

  View details for Web of Science ID 000232741900021

  View details for PubMedID 16237312

• FDG PET-CT demonstration of Sjogren's sialoadenitis CLINICAL NUCLEAR MEDICINE Jadvar, H., Bonyadlou, S., Iagaru, A., Colletti, P. M. 2005; 30 (10): 698-699

  Abstract

  We report the positron emission tomography-computed axial tomography (PET-CT) appearance of the inflammatory involvement of the salivary glands of a 69-year-old female with a history of lymphoma and known primary Sjogren's syndrome. Hybrid PET-CT was performed 5 months after completion of chemotherapy using a Siemens Biograph scanner (Knoxville, TN) 45 minutes after intravenous administration of 15 mCi of F-18 fluorodeoxyglucose (FDG). CT transmission scan was obtained for attenuation correction. PET-CT demonstrated no evidence of hypermetabolic nodal disease but showed symmetric intensely hypermetabolic submandibular and parotid salivary glands.

  View details for Web of Science ID 000232048400016

  View details for PubMedID 16166849