Hong Song, MD, PhD

All Publications

• Analysing the tumor transcriptome of prostate cancer to predict efficacy of Lu-PSMA therapy. Journal for immunotherapy of cancer Handke, A., Kesch, C., Fendler, W. P., Telli, T., Liu, Y., Hakansson, A., Davicioni, E., Hughes, J., Song, H., Lueckerath, K., Herrmann, K., Hadaschik, B., Seifert, R. 2023; 11 (10)

  Abstract

  177Lu-PSMA ([177Lu]Lutetium-PSMA-617) therapy is an effective treatment option for patients with prostate specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer, but still shows a non-responder rate of approximately 30%. Combination regimes of programmed death-ligand 1 (PD-L1) inhibition and concomitant 177Lu-PSMA therapy have been proposed to increase the response rate. However, the interplay of immune landscape and 177Lu-PSMA therapy efficacy is poorly understood.Between March 2018 and December 2021, a total of 168 patients were referred to 177Lu-PSMA therapy in our department and received a mean total dose of 21.9 GBq (three cycles in mean). All patients received baseline PSMA positron emission tomography to assess the PSMA uptake. The histopathological specimen of the primary prostate tumor was available with sufficient RNA passing quality control steps for genomic analysis in n=23 patients. In this subset of patients, tumor RNA transcriptomic analyses assessed 74 immune-related features in total, out of which n=24 signatures were not co-correlated and investigated further for outcome prognostication.In the subset of patients who received 177Lu-PSMA therapy, PD-L1 was not significantly associated with OS (HR per SD change (95% CI) 0.74 (0.42 to 1.30); SD: 0.18; p=0.29). In contrast, PD-L2 signature was positively associated with longer OS (HR per SD change 0.46 (95% CI 0.29 to 0.74); SD: 0.24; p=0.001; median OS 17.2 vs 5.7 months in higher vs lower PD-L2 patients). In addition, PD-L2 signature correlated with PSA-response (ϱ=-0.46; p=0.04). The PD-L2 signature association with OS was significantly moderated by L-Lactatdehydrogenase (LDH) levels (Cox model interaction p=0.01).Higher PD-L2 signature might be associated with a better response to 177Lu-PSMA therapy and warrants further studies investigating additional immunotherapy. In contrast, PD-L1 was not associated with outcome. The protective effect of PD-L2 signature might be present only in men with lower LDH levels.

  View details for DOI 10.1136/jitc-2023-007354

  View details for PubMedID 37857524

• 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

• 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

• 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

• 64Cu-DOTATATE Uptake in a Pulmonary Hamartoma. Clinical nuclear medicine Song, H., Guja, K. E., Yang, E. J., Guo, H. H. 2023; 48 (1): 58-60

  Abstract

  DOTATATE PET/CT is frequently used to evaluate indeterminant pulmonary nodules suspected to be pulmonary carcinoid. We report an unexpected case of pulmonary hamartoma demonstrating 64Cu-DOTATATE uptake in a 43-year-old woman with a slowly enlarging pulmonary nodule. Histopathological staining showed somatostatin receptor 2 expression on vascular endothelial cells and a proportion of cartilage and smooth muscle cells within the hamartoma.

  View details for DOI 10.1097/RLU.0000000000004390

  View details for PubMedID 36469060

• Biodistribution of a Mitochondrial Metabolic Tracer, [18F]F-AraG, in Healthy Volunteers. Molecular imaging Levi, J., Duan, H., Yaghoubi, S., Packiasamy, J., Huynh, L., Lam, T., Shaikh, F., Behera, D., Song, H., Blecha, J., Jivan, S., Seo, Y., VanBrocklin, H. F. 2022; 2022: 3667417

  Abstract

  [18F]F-AraG is a radiolabeled nucleoside analog that shows relative specificity for activated T cells. The aim of this study was to investigate the biodistribution of [18F]F-AraG in healthy volunteers and assess the preliminary safety and radiation dosimetry.Six healthy subjects (three female and three male) between the ages of 24 and 60 participated in the study. Each subject received a bolus venous injection of [18F]F-AraG (dose range: 244.2-329.3 MBq) prior to four consecutive PET/MR whole-body scans. Blood samples were collected at regular intervals and vital signs monitored before and after tracer administration. Regions of interest were delineated for multiple organs, and the area under the time-activity curves was calculated for each organ and used to derive time-integrated activity coefficient (TIAC). TIACs were input for absorbed dose and effective dose calculations using OLINDA.PET/MR examination was well tolerated, and no adverse effects to the administration of [18F]F-AraG were noted by the study participants. The biodistribution was generally reflective of the expression and activity profiles of the enzymes involved in [18F]F-AraG's cellular accumulation, mitochondrial kinase dGK, and SAMHD1. The highest uptake was observed in the kidneys and liver, while the brain, lung, bone marrow, and muscle showed low tracer uptake. The estimated effective dose for [18F]F-AraG was 0.0162 mSv/MBq (0.0167 mSv/MBq for females and 0.0157 mSv/MBq for males).Biodistribution of [18F]F-AraG in healthy volunteers was consistent with its association with mitochondrial metabolism. PET/MR [18F]F-AraG imaging was well tolerated, with a radiation dosimetry profile similar to other commonly used [18F]-labeled tracers. [18F]F-AraG's connection with mitochondrial biogenesis and favorable biodistribution characteristics make it an attractive tracer with a variety of potential applications.

  View details for DOI 10.1155/2022/3667417

  View details for PubMedID 36072652

  View details for PubMedCentralID PMC9400547

• Results of First Interim Analysis of 68Ga-NeoB and 68Ga-PSMA R2 PET/MRI in Patients with Biochemically Recurrent Prostate Cancer Duan, H., Song, H., Davidzon, G., Moradi, F., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2022

  View details for Web of Science ID 000893739700242

• 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

• 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

• The other immuno-PET: Metabolic tracers in evaluation of immune responses to immune checkpoint inhibitor therapy for solid tumors. Frontiers in immunology Levi, J., Song, H. 2022; 13: 1113924

  Abstract

  Unique patterns of response to immune checkpoint inhibitor therapy, discernable in the earliest clinical trials, demanded a reconsideration of the standard methods of radiological treatment assessment. Immunomonitoring, that characterizes immune responses, offers several significant advantages over the tumor-centric approach currently used in the clinical practice: 1) better understanding of the drugs' mechanism of action and treatment resistance, 2) earlier assessment of response to therapy, 3) patient/therapy selection, 4) evaluation of toxicity and 5) more accurate end-point in clinical trials. PET imaging in combination with the right agent offers non-invasive tracking of immune processes on a whole-body level and thus represents a method uniquely well-suited for immunomonitoring. Small molecule metabolic tracers, largely neglected in the immuno-PET discourse, offer a way to monitor immune responses by assessing cellular metabolism known to be intricately linked with immune cell function. In this review, we highlight the use of small molecule metabolic tracers in imaging immune responses, provide a view of their value in the clinic and discuss the importance of image analysis in the context of tracking a moving target.

  View details for DOI 10.3389/fimmu.2022.1113924

  View details for PubMedID 36700226

• 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

• 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

• 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

• 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

• 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

• Combined "One Stop Shop" NaF/FDG PET/MRI Evaluation of Response to Xofigo (R) in mCRPC Patients Song, H., Yohannan, T., Srinivas, S., Vasanawala, S., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2018

  View details for Web of Science ID 000467489902151