Lucia Baratto

All Publications

• Improved Detection of Bone Metastases in Children and Young Adults with Ferumoxytol-enhanced MRI. Radiology. Imaging cancer Rashidi, A., Baratto, L., Theruvath, A. J., Greene, E. B., Jayapal, P., Hawk, K. E., Lu, R., Seekins, J., Spunt, S. L., Pribnow, A., Daldrup-Link, H. E. 2023; 5 (2): e220080

  Abstract

  Purpose To evaluate if ferumoxytol can improve the detection of bone marrow metastases at diffusion-weighted (DW) MRI in pediatric and young adult patients with cancer. Materials and Methods In this secondary analysis of a prospective institutional review board-approved study (ClinicalTrials.gov identifier NCT01542879), 26 children and young adults (age range: 2-25 years; 18 males) underwent unenhanced or ferumoxytol-enhanced whole-body DW MRI between 2015 and 2020. Two reviewers determined the presence of bone marrow metastases using a Likert scale. One additional reviewer measured signal-to-noise ratios (SNRs) and tumor-to-bone marrow contrast. Fluorine 18 (18F) fluorodeoxyglucose (FDG) PET and follow-up chest CT, abdominal and pelvic CT, and standard (non-ferumoxytol enhanced) MRI served as the reference standard. Results of different experimental groups were compared using generalized estimation equations, Wilcoxon rank sum test, and Wilcoxon signed rank test. Results The SNR of normal bone marrow was significantly lower at ferumoxytol-enhanced MRI compared with unenhanced MRI at baseline (21.380 ± 19.878 vs 102.621 ± 94.346, respectively; P = .03) and after chemotherapy (20.026 ± 7.664 vs 54.110 ± 48.022, respectively; P = .006). This led to an increased tumor-to-marrow contrast on ferumoxytol-enhanced MRI scans compared with unenhanced MRI scans at baseline (1397.474 ± 938.576 vs 665.364 ± 440.576, respectively; P = .07) and after chemotherapy (1099.205 ± 864.604 vs 500.758 ± 439.975, respectively; P = .007). Accordingly, the sensitivity and diagnostic accuracy for detecting bone marrow metastases were 96% (94 of 98) and 99% (293 of 297), respectively, with the use of ferumoxytol-enhanced MRI compared with 83% (106 of 127) and 95% (369 of 390) with the use of unenhanced MRI. Conclusion Use of ferumoxytol helped improve the detection of bone marrow metastases in children and young adults with cancer. Keywords: Pediatrics, Molecular Imaging-Cancer, Molecular Imaging-Nanoparticles, MR-Diffusion Weighted Imaging, MR Imaging, Skeletal-Appendicular, Skeletal-Axial, Bone Marrow, Comparative Studies, Cancer Imaging, Ferumoxytol, USPIO © RSNA, 2023 ClinicalTrials.gov registration no. NCT01542879 See also the commentary by Holter-Chakrabarty and Glover in this issue.

  View details for DOI 10.1148/rycan.220080

  View details for PubMedID 36999999

• 18F-FDG PET/MRI AND DIFFUSION-WEIGHTED MRI FOR STAGING AND TREATMENT MONITORING OF LANGERHANS CELL HISTIOCYTOSIS IN CHILDREN Jeng, M., Baratto, L., Nyalakonda, R., Theruvath, A., Rashidi, A., Sundaram, V., States, L., Aboian, M., Daldrup-Link, H. E. WILEY. 2023: S24-S25

  View details for Web of Science ID 000904088900053

• Comparison of whole-body DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis. European journal of nuclear medicine and molecular imaging Baratto, L., Nyalakonda, R., Theruvath, A. J., Sarrami, A. H., Hawk, K. E., Rashidi, A., Shen, S., States, L., Aboian, M., Jeng, M., Daldrup-Link, H. E. 2023

  Abstract

  PURPOSE: To assess and compare the diagnostic accuracy of whole-body (WB) DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis (LCH).METHODS: Twenty-three children with LCH underwent 2-[18F]FDG PET and WB DW-MRI at baseline. Two nuclear medicine physicians and two radiologists independently assessed presence/absence of tumors in 8 anatomical areas. Sixteen children also performed 2-[18F]FDG PET and WB DW-MRI at follow-up. One radiologist and one nuclear medicine physician revised follow-up scans and collected changes in tumor apparent diffusion (ADC) and standardized uptake values (SUV) before and after therapy in all detectable lesions. 2-[18F]FDG PET results were considered the standard of reference for tumor detection and evaluation of treatment response according to Lugano criteria. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of WB DW-MRI at baseline were calculated, and the 95% confidence intervals were estimated by using the Clopper-Pearson (exact) method; changes in tumor SUVs and ADC were compared using a Mann-Whitney U test. Agreement between reviewers was assessed with a Cohen's weighted kappa coefficient. Analyses were conducted using SAS software version 9.4.RESULTS: Agreement between reviewers was perfect (kappa coefficient=1) for all analyzed regions but spine and neck (kappa coefficient=0.89 and 0.83, respectively) for 2-[18F]FDG PET images, and abdomen and pelvis (kappa coefficient=0.65 and 0.88, respectively) for WB DW-MRI. Sensitivity and specificity were 95.5% and 100% for WB DW-MRI compared to 2-[18F]FDG PET. Pre to post-treatment changes in SUVratio and ADCmean were inversely correlated for all lesions (r: -0.27, p=0·06) and significantly different between responders and non-responders to chemotherapy (p=0.0006 and p=0·003 for SUVratio and ADCmean, respectively).CONCLUSION: Our study showed that WB DW-MRI has similar accuracy to 2-[18F]FDG PET for staging and treatment monitoring of LCH in children. While 2-[18F]FDG PET remains an approved radiological examination for assessing metabolically active disease, WB DW-MRI could be considered as an alternative approach without radiation exposure. The combination of both modalities might have advantages over either approach alone.

  View details for DOI 10.1007/s00259-023-06122-6

  View details for PubMedID 36717409

• Detection of bone marrow metastases in children and young adults with solid cancers with diffusion-weighted MRI. Skeletal radiology Rashidi, A., Baratto, L., Jayapal, P., Theruvath, A. J., Greene, E. B., Lu, R., Spunt, S. L., Daldrup-Link, H. E. 2022

  Abstract

  OBJECTIVE: To compare the diagnostic accuracy of diffusion-weighted (DW)-MRI with b-values of 50s/mm2 and 800s/mm2 for the detection of bone marrow metastases in children and young adults with solid malignancies.METHODS: In an institutional review board-approved prospective study, we performed 51 whole-body DW-MRI scans in 19 children and young adults (14 males, 5 females; age range: 1-25years) with metastasized cancers before (n=19 scans) and after (n=32 scans) chemotherapy. Two readers determined the presence of focal bone marrow lesions in 10 anatomical areas. A third reader measured ADC and SNR of focal lesions and normal marrow. Simultaneously acquired 18F-FDG-PET scans served as the standard of reference. Data of b=50s/mm2 and 800s/mm2 images were compared with the Wilcoxon signed-rank test. Inter-reader agreement was evaluated with weighted kappa statistics.RESULTS: The SNR of bone marrow metastases was significantly higher compared to normal bone marrow on b=50s/mm2 (mean±SD: 978.436±1239.436 vs. 108.881±109.813, p<0.001) and b=800s/mm2 DW-MRI (499.638±612.721 vs. 86.280±89.120; p<0.001). On 30 out of 32 post-treatment DW-MRI scans, reconverted marrow demonstrated low signal with low ADC values (0.385*10-3±0.168*10-3mm2/s). The same number of metastases (556/588; 94.6%; p>0.99) was detected on b=50s/mm2 and 800s/mm2 images. However, both normal marrow and metastases exhibited low signals on ADC maps, limiting the ability to delineate metastases. The inter-reader agreement was substantial, with a weighted kappa of 0.783 and 0.778, respectively.CONCLUSION: Bone marrow metastases in children and young adults can be equally well detected on b=50s/mm2 and 800s/mm2 images, but ADC values can be misleading.

  View details for DOI 10.1007/s00256-022-04240-0

  View details for PubMedID 36441237

• FLIPI-3: A New PET-Based Prognostic Index for Follicular Lymphoma Based on Results from a Validation Study with the ECOG-ACRIN E2408 Cohort St-Pierre, F., Broski, S., Sun, Z., Kocherginsky, M., Quon, A., Baratto, L., Savas, H., Kostakoglu, L., Winter, J. N., Witzig, T. E., Kahl, B. S., Evens, A., Gordon, L. AMER SOC HEMATOLOGY. 2022: 6480-6481

  View details for DOI 10.1182/blood-2022-162114

  View details for Web of Science ID 000893223206221

• Ferumoxytol-Enhanced MRI in Children and Young Adults: State of the Art. AJR. American journal of roentgenology Adams, L. C., Jayapal, P., Ramasamy, S. K., Morakote, W., Yeom, K., Baratto, L., Daldrup-Link, H. E. 2022

  Abstract

  Ferumoxytol is an ultrasmall iron oxide nanoparticle, originally approved in 2009 by the FDA for IV treatment of iron deficiency in adults with chronic kidney disease. Subsequently, its off-label use as an MRI contrast agent has increased in clinical practice, particularly in pediatric patients in North America. Unlike conventional MRI contrast agents that are based on the rare earth metal gadolinium [gadolinium-based contrast agents (GBCAs)], ferumoxytol is biodegradable and carries no potential risk of nephrogenic systemic fibrosis. At FDA-approved doses, ferumoxytol demonstrates no long-term tissue retention in patients with intact iron metabolism. Ferumoxytol provides unique MRI properties including long-lasting vascular retention (facilitating high-quality vascular imaging) and retention in reticuloendothelial system tissues, thereby supporting a variety of applications beyond those possible with GBCAs. This Clinical Perspective describes clinical and early translational applications of ferumoxytol-enhanced MRI in children and young adults through off-label use for a variety of settings, including vascular, cardiac, and cancer imaging, drawing on the authors' institutional experience. In addition, we describe current preclinical and clinical research advances using ferumoxytol with regard to cellular and molecular imaging, and also as a novel potential cancer therapeutic agent.

  View details for DOI 10.2214/AJR.22.28453

  View details for PubMedID 36197052

• PET/MR of pediatric bone tumors: what the radiologist needs to know. Skeletal radiology Padwal, J., Baratto, L., Chakraborty, A., Hawk, K., Spunt, S., Avedian, R., Daldrup-Link, H. E. 2022

  Abstract

  Integrated 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG) positron emission tomography (PET)/magnetic resonance (MR) imaging can provide "one stop" local tumor and whole-body staging in one session, thereby streamlining imaging evaluations and avoiding duplicate anesthesia in young children. 18F-FDG PET/MR scans have the benefit of lower radiation, superior soft tissue contrast, and increased patient convenience compared to 18F-FDG PET/computerized tomography scans. This article reviews the 18F-FDG PET/MR imaging technique, reporting requirements, and imaging characteristics of the most common pediatric bone tumors, including osteosarcoma, Ewing sarcoma, primary bone lymphoma, bone and bone marrow metastases, and Langerhans cell histiocytosis.

  View details for DOI 10.1007/s00256-022-04113-6

  View details for PubMedID 35804163

• PET AND MRI IMAGING-BASED AI MODELS IN PEDIATRIC ONCOLOGY Baratto, L., Wang, Y., Theruvath, A., Sarrami, A., Sheybani, N., Hawk, K., Daldrup-Link, H. SOC NUCLEAR MEDICINE INC. 2022

  View details for Web of Science ID 000893739700076

• 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

• Diagnostic Accuracy of 2-[18F]FDG-PET and whole-body DW-MRI for the detection of bone marrow metastases in children and young adults. European radiology Rashidi, A., Baratto, L., Theruvath, A. J., Greene, E. B., Hawk, K. E., Lu, R., Link, M. P., Spunt, S. L., Daldrup-Link, H. E. 1800

  Abstract

  OBJECTIVES: To compare the diagnostic accuracy of 2-[18F]fluoro-2-deoxy-D-glucose-enhanced positron emission tomography (2-[18F]FDG-PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) for the detection of bone marrow metastases in children and young adults with solid malignancies.METHODS: In this cross-sectional single-center institutional review board-approved study, we investigated twenty-three children and young adults (mean age, 16.8years±5.1 [standard deviation]; age range, 7-25years; 16 males, 7 females) with 925 bone marrow metastases who underwent 66 simultaneous 2-[18F]FDG-PET and DW-MRI scans including 23 baseline scans and 43 follow-up scans after chemotherapy between May 2015 and July 2020. Four reviewers evaluated all foci of bone marrow metastasis on 2-[18F]FDG-PET and DW-MRI to assess concordance and measured the tumor-to-bone marrow contrast. Results were assessed with a one-sample Wilcoxon test and generalized estimation equation. Bone marrow biopsies and follow-up imaging served as the standard of reference.RESULTS: The reviewers detected 884 (884/925, 95.5%) bone marrow metastases on 2-[18F]FDG-PET and 893 (893/925, 96.5%) bone marrow metastases on DW-MRI. We found different "blind spots" for 2-[18F]FDG-PET and MRI: 2-[18F]FDG-PET missed subcentimeter lesions while DW-MRI missed lesions in small bones. Sensitivity and specificity were 91.0% and 100% for 18F-FDG-PET, 89.1% and 100.0% for DW-MRI, and 100.0% and 100.0% for combined modalities, respectively. The diagnostic accuracy of combined 2-[18F]FDG-PET/MRI (100.0%) was significantly higher compared to either 2-[18F]FDG-PET (96.9%, p<0.001) or DW-MRI (96.3%, p<0.001).CONCLUSIONS: Both 2-[18F]FDG-PET and DW-MRI can miss bone marrow metastases. The combination of both imaging techniques detected significantly more lesions than either technique alone.KEY POINTS: DW-MRI and 2-[18F]FDG-PET have different strengths and limitations for the detection of bone marrow metastases in children and young adults with solid tumors. Both modalities can miss bone marrow metastases, although the "blind spot" of each modality is different. A combined PET/MR imaging approach will achieve maximum sensitivity and specificity for the detection of bone marrow metastases in children with solid tumors.

  View details for DOI 10.1007/s00330-021-08529-x

  View details for PubMedID 35099603

• 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

• PET/MRI Improves Management of Children with Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Baratto, L., Hawk, K. E., States, L., Qi, J., Gatidis, S., Kiru, L., Daldrup-Link, H. E. 2021; 62 (10): 1334-1340

  Abstract

  Integrated PET/MRI has shown significant clinical value for staging and restaging of children with cancer by providing functional and anatomic tumor evaluation with a 1-stop imaging test and with up to 80% reduced radiation exposure compared with 18F-FDG PET/CT. This article reviews clinical applications of 18F-FDG PET/MRI that are relevant for pediatric oncology, with particular attention to the value of PET/MRI for patient management. Early adopters from 4 different institutions share their insights about specific advantages of PET/MRI technology for the assessment of young children with cancer. We discuss how whole-body PET/MRI can be of value in the evaluation of certain anatomic regions, such as soft tissues and bone marrow, as well as specific PET/MRI interpretation hallmarks in pediatric patients. We highlight how whole-body PET/MRI can improve the clinical management of children with lymphoma, sarcoma, and neurofibromatosis, by reducing the number of radiologic examinations needed (and consequently the radiation exposure), without losing diagnostic accuracy. We examine how PET/MRI can help in differentiating malignant tumors versus infectious or inflammatory diseases. Future research directions toward the use of PET/MRI for treatment evaluation of patients undergoing immunotherapy and assessment of different theranostic agents are also briefly explored. Lessons learned from applications in children might also be extended to evaluations of adult patients.

  View details for DOI 10.2967/jnumed.120.259747

  View details for PubMedID 34599010

• 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

• 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

• 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

• 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

• 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

• Imaging Chemotherapy-Induced Brain Damage in Pediatric Cancer Survivors Baratto, L., Garcia, D., Rashidi, A., Iv, M., Hawk, K., Daldrup-Link, H. SOC NUCLEAR MEDICINE INC. 2021

  View details for Web of Science ID 000713713600088

• One-stop local and whole-body staging of children with cancer. Pediatric radiology Daldrup-Link, H. E., Theruvath, A. J., Baratto, L., Hawk, K. E. 2021

  Abstract

  Accurate staging and re-staging of cancer in children is crucial for patient management. Currently, children with a newly diagnosed cancer must undergo a series of imaging tests, which are stressful, time-consuming, partially redundant, expensive, and can require repetitive anesthesia. New approaches for pediatric cancer staging can evaluate the primary tumor and metastases in a single session. However, traditional one-stop imaging tests, such as CT and positron emission tomography (PET)/CT, are associated with considerable radiation exposure. This is particularly concerning for children because they are more sensitive to ionizing radiation than adults and they live long enough to experience secondary cancers later in life. In this review article we discuss child-tailored imaging tests for tumor detection and therapy response assessment - tests that can be obtained with substantially reduced radiation exposure compared to traditional CT and PET/CT scans. This includes diffusion-weighted imaging (DWI)/MRI and integrated [F-18]2-fluoro-2-deoxyglucose (18F-FDG) PET/MRI scans. While several investigators have compared the value of DWI/MRI and 18F-FDG PET/MRI for staging pediatric cancer, the value of these novel imaging technologies for cancer therapy monitoring has received surprisingly little attention. In this article, we share our experiences and review existing literature on this subject.

  View details for DOI 10.1007/s00247-021-05076-x

  View details for PubMedID 33929564

• Correlation of 18-fluorodeoxyglucose PET/computed tomography parameters and clinical features to predict outcome for diffuse large B-cell lymphoma. Nuclear medicine communications Baratto, L., Wu, F., Minamimoto, R., Hatami, N., Liang, T., Sabile, J., Advani, R. H., Mittra, E. 2021

  Abstract

  PURPOSE: To determine if the correlation between different metabolic parameters along with clinical features can create an improved model of prognostication for diffuse large B-cell lymphoma (DLBCL) patients.METHODS: We retrospectively evaluated 89 patients with DLBCL. All patients had a baseline and an interim 18F-FDG PET/CT. Seventy-nine also had an end-of-treatment PET/CT (EOT-PET). For each scan, we collected standardized uptake value (SUVmax, SUVmean, SUVpeak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVmaxsum, SUVmeansum, MTVsum, and TLGsum. These metabolic parameters were combined with clinical features in order to identify a new prognostic model. The predictive value of interim PET and EOT-PET using Deauville score was also determined.RESULTS: Baseline SUVmaxsum and SUVmeansum were significantly correlated to overall survival (OS) (P value=0.012 and 0.011, respectively). The percentage change of MTV and TLG sum from baseline to EOT was predictive of progression-free survival (PFS) (P value=0.003 and 0.022, respectively). The combination of either Deauville score at the EOT and SUVmaxsum at baseline significantly predicted OS (P value <0.001); Eastern Cooperative Oncology Group performance status, presence of extranodal disease and percentage change of MTVsum from baseline to EOT were significant predictors of PFS (P value=0.001).CONCLUSIONS: SUVmaxsum and SUVmeansum at baseline and percentage change in MTV and TLG sum from baseline to EOT are predictors of outcome in DLBCL patients. These metabolic parameters combined to Deauville score and some clinical features could be used together to stratify patients.

  View details for DOI 10.1097/MNM.0000000000001398

  View details for PubMedID 33741852

• 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

• Artificial intelligence enables whole-body positron emission tomography scans with minimal radiation exposure. European journal of nuclear medicine and molecular imaging Wang, Y. J., Baratto, L., Hawk, K. E., Theruvath, A. J., Pribnow, A., Thakor, A. S., Gatidis, S., Lu, R., Gummidipundi, S. E., Garcia-Diaz, J., Rubin, D., Daldrup-Link, H. E. 2021

  Abstract

  PURPOSE: To generate diagnostic 18F-FDG PET images of pediatric cancer patients from ultra-low-dose 18F-FDG PET input images, using a novel artificial intelligence (AI) algorithm.METHODS: We used whole-body 18F-FDG-PET/MRI scans of 33 children and young adults with lymphoma (3-30years) to develop a convolutional neural network (CNN), which combines inputs from simulated 6.25% ultra-low-dose 18F-FDG PET scans and simultaneously acquired MRI scans to produce a standard-dose 18F-FDG PET scan. The image quality of ultra-low-dose PET scans, AI-augmented PET scans, and clinical standard PET scans was evaluated by traditional metrics in computer vision and by expert radiologists and nuclear medicine physicians, using Wilcoxon signed-rank tests and weighted kappa statistics.RESULTS: The peak signal-to-noise ratio and structural similarity index were significantly higher, and the normalized root-mean-square error was significantly lower on the AI-reconstructed PET images compared to simulated 6.25% dose images (p<0.001). Compared to the ground-truth standard-dose PET, SUVmax values of tumors and reference tissues were significantly higher on the simulated 6.25% ultra-low-dose PET scans as a result of image noise. After the CNN augmentation, the SUVmax values were recovered to values similar to the standard-dose PET. Quantitative measures of the readers' diagnostic confidence demonstrated significantly higher agreement between standard clinical scans and AI-reconstructed PET scans (kappa=0.942) than 6.25% dose scans (kappa=0.650).CONCLUSIONS: Our CNN model could generate simulated clinical standard 18F-FDG PET images from ultra-low-dose inputs, while maintaining clinically relevant information in terms of diagnostic accuracy and quantitative SUV measurements.

  View details for DOI 10.1007/s00259-021-05197-3

  View details for PubMedID 33527176

• 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

• Increasing Diversity in Radiology and Molecular Imaging: Current Challenges. Molecular imaging and biology Fite, B. Z., Hinostroza, V. n., States, L. n., Hicks-Nelson, A. n., Baratto, L. n., Kallianos, K. n., Codari, M. n., Yu, B. n., Jha, P. n., Shams, M. n., Stoyanova, T. n., Chapelin, F. F., Liu, A. n., Rashidi, A. n., Soto, F. n., Quintana, Y. n., Davidzon, G. A., Marycz, K. n., Gibbs, I. C., Chonde, D. B., Patel, C. B., Daldrup-Link, H. E. 2021

  Abstract

  This paper summarizes the 2020 Diversity in Radiology and Molecular Imaging: What We Need to Know Conference, a three-day virtual conference held September 9-11, 2020. The World Molecular Imaging Society (WMIS) and Stanford University jointly organized this event to provide a forum for WMIS members and affiliates worldwide to openly discuss issues pertaining to diversity in science, technology, engineering, and mathematics (STEM). The participants discussed three main conference themes, "racial diversity in STEM," "women in STEM," and "global health," which were discussed through seven plenary lectures, twelve scientific presentations, and nine roundtable discussions, respectively. Breakout sessions were designed to flip the classroom and seek input from attendees on important topics such as increasing the representation of underrepresented minority (URM) members and women in STEM, generating pipeline programs in the fields of molecular imaging, supporting existing URM and women members in their career pursuits, developing mechanisms to effectively address microaggressions, providing leadership opportunities for URM and women STEM members, improving global health research, and developing strategies to advance culturally competent healthcare.

  View details for DOI 10.1007/s11307-021-01610-3

  View details for PubMedID 33903986

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• Predicting Response to Immunotherapy by Evaluating Tumors, Lymphoid Cell-Rich Organs, and Immune-Related Adverse Events Using FDG-PET/CT. Clinical nuclear medicine Nobashi, T., Baratto, L., Reddy, S. A., Srinivas, S., Toriihara, A., Hatami, N., Yohannan, T. K., Mittra, E. 2019

  Abstract

  PURPOSE: To investigate whether the evaluation of tumors, lymphoid cell-rich organs, and immune-related adverse events (IRAE) with F-FDG PET/CT can predict the efficacy and outcome of immunotherapy.METHODS: Forty patients who underwent F-FDG-PET/CT scans before and after therapy with immune checkpoint inhibitors from December 2013 to December 2016 were retrospectively enrolled (malignant melanoma, n = 21; malignant lymphoma, n = 11; renal cell carcinoma, n = 8). SUVmax of the baseline and first restaging scans were evaluated in tumors, spleen, bone marrow, thyroid and pituitary glands, and were correlated to best overall response in the first year after therapy; IRAE-affected areas were also evaluated.RESULTS: Interval change between the baseline and first restaging scans showed that patients with a clinical benefit had a significant decrease in tumor parameters (P < 0.001). All patients with an increase of SUVmax in the thyroid of more than 1.5 (n = 5) on the first restaging scan had a complete response (CR) in 1 year. Patients with CR within 1 year (n = 22) were significantly associated with a favorable long-term outcome (P = 0.002). Nine patients with IRAE findings had CR at final evaluation. Among IRAE, thyroiditis was seen significantly earlier than arthritis (P = 0.040).CONCLUSIONS: The decrease of tumor parameters at early time-point PET scans was seen in patients with immunotherapy who had clinical benefit within 1 year. PET-detectable IRAE was useful for prediction of a favorable outcome. Early development of thyroiditis may particularly represent an early response indicator to immunotherapy.

  View details for PubMedID 30688730

• 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

• 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

• 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

• The Prognostic Impact of Baseline Positron Emission Tomography (PET) Imaging in Untreated High Risk (HR) Follicular Lymphoma (FL): Analysis from E2408, the Bortezomib Induction or Novel Imid (R) Continuation (BIONIC) Study Baratto, L., Jegede, O., Hong, F., Habermann, T. M., Advani, R., Gascoyne, R. D., Kostakoglu, L., Witzig, T. E., Ranheim, E. A., Kahl, B. S., Quon, A., Evens, A. M. AMER SOC HEMATOLOGY. 2018

  View details for DOI 10.1182/blood-2018-99-113247

  View details for Web of Science ID 000454837605004

• 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

• End-of-treatment and serial PET imaging in primary mediastinal B-cell lymphoma following dose-adjusted EPOCH-R: a paradigm shift in clinical decision making HAEMATOLOGICA Melani, C., Advani, R., Roschewski, M., Walters, K. M., Chen, C. C., Baratto, L., Ahlman, M. A., Miljkovic, M. D., Steinberg, S. M., Lam, J., Shovlin, M., Dunleavy, K., Pittaluga, S., Jaffe, E. S., Wilson, W. H. 2018; 103 (8): 1337–44

  Abstract

  Dose-adjusted-EPOCH-R obviates the need for radiotherapy in most patients with primary mediastinal B-cell lymphoma. End-of-treatment PET, however, does not accurately identify patients at risk of treatment failure, thereby confounding clinical decision making. To define the role of PET in primary mediastinal B-cell lymphoma following dose-adjusted-EPOCH-R, we extended enrollment and follow up on our published phase II trial and independent series. Ninety-three patients received dose-adjusted-EPOCH-R without radiotherapy. End-of-treatment PET was performed in 80 patients, of whom 57 received 144 serial scans. One nuclear medicine physician from each institution blindly reviewed all scans from their respective institution. End-of-treatment PET was negative (Deauville 1-3) in 55 (69%) patients with one treatment failure (8-year event-free and overall survival of 96.0% and 97.7%). Among 25 (31%) patients with a positive (Deauville 4-5) end-of-treatment PET, there were 5 (20%) treatment failures (8-year event-free and overall survival of 71.1% and 84.3%). Linear regression analysis of serial scans showed a significant decrease in SUVmax in positive end-of-treatment PET non-progressors compared to an increase in treatment failures. Among 6 treatment failures, the median end-of-treatment SUVmax was 15.4 (range, 1.9-21.3), and 4 achieved long-term remission with salvage therapy. Virtually all patients with a negative end-of-treatment PET following dose-adjusted-EPOCH-R achieved durable remissions and should not receive radiotherapy. Among patients with a positive end-of-treatment PET, only 5/25 (20%) had treatment-failure. Serial PET imaging distinguished end-of-treatment PET positive patients without treatment failure, thereby reducing unnecessary radiotherapy by 80%, and should be considered in all patients with an initial positive PET following dose-adjusted-EPOCH-R (clinicaltrials.gov identifier 00001337).

  View details for PubMedID 29748435

• 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

• 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

• Sentinel node biopsy in endometrial cancer: an update CLINICAL AND TRANSLATIONAL IMAGING Crivellaro, C., Baratto, L., Dolci, C., De Ponti, E., Magni, S., Elisei, F., Papadia, A., Buda, A. 2018; 6 (2): 91–100

  View details for DOI 10.1007/s40336-018-0268-9

  View details for Web of Science ID 000429373500003

• 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

• Role of Imaging in Early-Phase Trials NOVEL DESIGNS OF EARLY PHASE TRIALS FOR CANCER THERAPEUTICS Greene, L., Srinivas, S., Park, S., Hatami, N., Nobashi, T., Baratto, L., Toriihara, A., Gambhir, S. S., Kummar, S., Takimoto, C. 2018: 129–49

  View details for DOI 10.1016/B978-0-12-812512-0.00010-5

  View details for Web of Science ID 000464871500011

• 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

• 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