Same-day post-therapy imaging with a new generation whole-body digital SPECT/CT in assessing treatment response to [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer.

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

ACR-ACNM-ARS-ASTRO-SNMMI Practice Parameter for the Performance of Therapy With Radiopharmaceuticals.

OBJECTIVES: This practice parameter was revised collaboratively by the American College of Radiology (ACR), the American College of Nuclear Medicine, the American Radium Society, the American Society for Radiation Oncology, and the Society of Nuclear Medicine and Molecular Imaging. The document is intended to serve as a resource for appropriately trained and licensed physicians who perform therapeutic procedures with unsealed sources, referred to in the document using the more inclusive terminology of radiopharmaceuticals, for which a written directive is required for authorized users under NRC 10 CFR 35.300. METHODS: This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website ( https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards ) by the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the American Radium Society. RESULTS: This practice parameter addresses the overall role of the applicable physician-authorized user, Qualified Medical Physicist, and other specialized personnel involved in the delivery of radiopharmaceutical therapy. Therapeutic radiopharmaceuticals include those administered as elemental radioactive isotopes (radionuclides) or the radioactive element incorporated into a targeting molecule (ligand) by one or more chemical bonds. This document provides guidance regarding general principles of radionuclide therapies and indications of various alpha, beta, gamma, and mixed emission agents with references to several recent practice parameters on new and commonly performed radiopharmaceutical therapies. CONCLUSION: This document addresses clinical circumstances, elements of available agents, and the qualifications and responsibilities of various members of the radiation care team, specifications of consultation and other clinical documentation, post-therapy follow-up, radiation safety precautions, elements of quality control and improvement programs, infection control, and patient education to ensure optimal patient care and safety when utilizing radiopharmaceuticals.

Definitive Treatment of Brain Metastases From a Neuroendocrine Tumor With Peptide Receptor Radionuclide Therapy With 177Lutetium DOTATATE: A Case Report.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare malignancies that arise from secretory endocrine cells of the gastroenteropancreatic system. Clinical outcomes have improved for patients with GEP-NETs due to the development and recent FDA approval of 177Lutetium DOTATATE. However, the response of brain metastases from GEP-NETs from 177Lutetium DOTATATE is unreported. We present the case of an 81-year-old man with low-grade small bowel GEP-NET with liver and brain metastases treated with a total of six cycles of 177Lutetium DOTATATE. With over three years of follow-up from his initial treatment, his brain metastases have had complete or partial responses, with no need for brain radiotherapy or radiosurgery.

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.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer.

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

A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Evaluation of Prostate Cancer Response to High-Intensity Focused Ultrasound Therapy.

Focal therapy for localized prostate cancer (PC) using high-intensity focused ultrasound (HIFU) is gaining in popularity as it is noninvasive and associated with fewer side effects than standard whole-gland treatments. However, better methods to evaluate response to HIFU ablation are an unmet need. Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors are both overexpressed in PC. In this study, we evaluated a novel approach of using both 68Ga-RM2 and 68Ga-PSMA11 PET/MRI in each patient before and after HIFU to assess the accuracy of target tumor localization and response to treatment. Methods: Fourteen men, 64.5 ± 8.0 y old (range, 48-78 y), with newly diagnosed PC were prospectively enrolled. Before HIFU, the patients underwent prostate biopsy, multiparametric MRI, 68Ga-PSMA11, and 68Ga-RM2 PET/MRI. Response to treatment was assessed at a minimum of 6 mo after HIFU with prostate biopsy (n = 13), as well as 68Ga-PSMA11 and 68Ga-RM2 PET/MRI (n = 14). The SUVmax and SUVpeak of known or suspected PC lesions were collected. Results: Pre-HIFU biopsy revealed 18 cancers, of which 14 were clinically significant (Gleason score ≥ 3 + 4). Multiparametric MRI identified 18 lesions; 14 of them were at least score 4 in the Prostate Imaging-Reporting and Data System. 68Ga-PSMA11 and 68Ga-RM2 PET/MRI each showed 23 positive intraprostatic lesions; 21 were congruent in 13 patients, and 5 were incongruent in 5 patients. Before HIFU, 68Ga-PSMA11 identified all target tumors, whereas 68Ga-RM2 PET/MRI missed 2 tumors. After HIFU, 68Ga-RM2 and 68Ga-PSMA11 PET/MRI both identified clinically significant residual disease in 1 patient. Three significant ipsilateral recurrent lesions were identified, whereas 1 was missed by 68Ga-PSMA11. The pretreatment level of prostate-specific antigen decreased significantly after HIFU, by 66%. Concordantly, the pretreatment SUVmax decreased significantly after HIFU for 68Ga-PSMA11 (P = 0.001) and 68Ga-RM2 (P = 0.005). Conclusion: This pilot study showed that 68Ga-PSMA11 and 68Ga-RM2 PET/MRI identified the target tumor for HIFU in 100% and 86% of cases, respectively, and accurately verified response to treatment. PET may be a useful tool in the guidance and monitoring of treatment success in patients receiving focal therapy for PC. These preliminary findings warrant larger studies for validation.

Striking Size Reduction of Rapidly Growing Pancreatic Neuroendocrine Carcinoma Metastatic Nodal Conglomerate After Only 2 Cycles of 177 Lu-DOTATATE.

ABSTRACT: Peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE has shown great treatment efficacy in patients with well-differentiated metastatic neuroendocrine tumors and a metastatic size reduction of ~20% for metastatic lesions <3 cm in size. We present a 66-year-old man with pancreatic neuroendocrine carcinoma, who had a rapidly growing metastatic nodal conglomerate, which measured close to 10 cm in size. After only 2 cycles of PRRT with 177 Lu-DOTATATE, the nodal conglomerate had a striking size reduction greater than 75%. This case highlights the potential efficacy of PRRT with 177 Lu-DOTATATE for treatment of aggressive neuroendocrine neoplasms.

Evaluation of Liver and Renal Toxicity in Peptide Receptor Radionuclide Therapy for Somatostatin Receptor Expressing Tumors: A 2-Year Follow-Up.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin receptor (SSR) analogs is now an established systemic treatment for neuroendocrine tumors (NET). However, more short- and long-term data about renal and hepatotoxicity is needed. Here we present our experience in this clinical scenario. METHODS: Eighty-six patients with progressive SSR-expressing malignancies underwent PRRT with Lu-177 Dotatate and were followed up for up to 2 years. Laboratory tests were done 1 week before each cycle and every 2 months at follow-up. Hepatic and renal toxicity was determined based on NCI CTCAE V5.0. RESULTS: 55/86 (64%) patients completed all 4 cycles of PRRT; 18/86 (20.9%) are currently being treated; 13/86 (15.1%) had to discontinue PRRT: 4/13 (31%) due to hematologic toxicity, 9/13 (69%) due to non-PRRT-related comorbidities. Out of the patients who finished treatment, only transient grade 2 toxicities were observed during PRRT: hypoalbuminemia in 5.5% (3/55), and renal toxicity (serum creatinine and estimated glomerular filtration rate) in 1.8% (1/55). No grade 3 or 4 liver and renal toxicity occurred. Patients presenting with impaired liver or renal function prior to PRRT, either improved or had stable findings. No deterioration was observed. CONCLUSION: Peptide receptor radionuclide therapy does not have a negative impact on liver and renal function, even in patients with pre-existing impaired parameters. No grade 3 or 4 hepatic or renal toxicity was identified. Only transient grade 2 hypoalbuminemia in 5.5% and nephrotoxicity in 1.8% of patients were seen during PRRT.

Radiotheranostics - Precision Medicine in Nuclear Medicine and Molecular Imaging.

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

Combined Quantification of 18F-FDG and 68Ga-DOTATATE PET/CT for Prognosis in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms.

RATIONALE AND OBJECTIVES: High-grade gastroenteropancreatic neuroendocrine neoplasms (G3 GEP-NENs) are pathologically classified into well differentiated neuroendocrine tumors (G3 NETs) and poorly differentiated neuroendocrine carcinomas (G3 NECs). Using a novel parameter, we examined the prognostic value of 18F-FDG and 68Ga-DOTATATE PET/CT quantification in comparison to pathologic assessment in G3 GEP-NENs. MATERIALS AND METHODS: A total of 31 patients with G3 GEP-NENs were reviewed. For each patient, the SUVmax on 18F-FDG and 68Ga-DOTATATE PET/CT were used to calculate the FDG-DOTATATE-Z (FDZ) score: a continuous parameter that increases with 68Ga-DOTATATE uptake and decreases with 18F-FDG uptake. The variation in the FDZ score with respect to pathologic variables was examined. Kaplan-Meier and Cox regression analyses were performed to evaluate the effect of FDZ score on overall survival. An external cohort of 21 patients was used for validation. RESULTS: The FDZ score was significantly higher in G3 NETs compared to G3 NECs (p<0.001), and was inversely correlated with Ki67 index (R2=0.33, p<0.001). Patients in the FDZ>0.05 group showed significantly longer survival compared to those in the FDZ≤0.05 group, with median of 34.9 vs. 12.0 months (p<0.001). On univariate regression, FDZ>0.05 (p=0.005), well differentiated disease (p=0.044), and lower Ki67 index (p=0.042) were predictors of survival. On multivariate regression, only FDZ>0.05 could independently predict longer survival with HR=0.16 (p=0.018), which was reproduced in the external validation cohort. CONCLUSION: Combined quantification of 18F-FDG and 68Ga-DOTATATE PET/CT into a novel parameter, the FDZ score, reflects the pathologic characteristics of G3 GEP-NENs and is a prognostic indicator of overall survival independent of differentiation.

68Ga-PSMA11 PET/CT for biochemically recurrent prostate cancer: Influence of dual-time and PMT- vs SiPM-based detectors.

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.

Neurovascular, Muscle, and Skin Changes on [18F]FDG PET/MRI in Complex Regional Pain Syndrome of the Foot: A Prospective Clinical Study.

OBJECTIVE: The goal of this study is to demonstrate the feasibility of simultaneous [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) for noninvasive visualization of muscular, neurovascular, and skin changes secondary to complex regional pain syndrome (CRPS). SUBJECTS: Seven adult patients with CRPS of the foot and seven healthy adult controls participated in our [18F]FDG PET/MRI study. METHODS: All participants received whole-body PET/MRI scans 1 hour after the injection of 370MBq [18F]FDG. Resulting PET/MRI images were reviewed by two radiologists. Metabolic and anatomic abnormalities identified, were grouped into muscular, neurovascular, and skin lesions. The [18F]FDG uptake of each lesion was compared with that of corresponding areas in controls using a Mann-Whitney U-test. RESULTS: On PET images, muscular abnormalities were found in five patients, neurovascular abnormalities in four patients, and skin abnormalities in two patients. However, on MRI images, no muscular abnormalities were detected. Neurovascular abnormalities and skin abnormalities in the affected limb were identified on MRI in one and two patients, respectively. The difference in [18F]FDG uptake between the patients and the controls was significant in muscle (P = .018) and neurovascular bundle (P = .0005). CONCLUSIONS: The increased uptake of [18F]FDG in the symptomatic areas likely reflects the increased metabolism due to the inflammatory response causing pain. Therefore, our approach combining metabolic [18F]FDG PET and anatomic MR imaging may offer noninvasive monitoring of the distribution and progression of inflammatory changes associated with CRPS.

Results of a Prospective Trial to Compare 68Ga-DOTA-TATE with SiPM-Based PET/CT vs. Conventional PET/CT in Patients with Neuroendocrine Tumors.

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.

High-Specific-Activity-131I-MIBG versus 177Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma.

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

Prognostic Value of Bone Marrow Metabolism on Pretreatment 18F-FDG PET/CT in Patients with Metastatic Melanoma Treated with Anti-PD-1 Therapy.

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

The Clinical Utility of 18F-Fluciclovine PET/CT in Biochemically Recurrent Prostate Cancer: an Academic Center Experience Post FDA Approval.

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

Sigma-1 Receptor Changes Observed in Chronic Pelvic Pain Patients: A Pilot PET/MRI Study.

Introduction: Chronic pelvic pain is a highly prevalent pain condition among women, but identifying the exact cause of pelvic pain remains a significant diagnostic challenge. In this study, we explored a new diagnostic approach with PET/MRI of the sigma-1 receptor, a chaperone protein modulating ion channels for activating nociceptive processes. Methods: Our approach is implemented by a simultaneous PET/MRI scan with a novel radioligand [18F]FTC-146, which is highly specific to the sigma-1 receptor. We recruited 5 chronic pelvic pain patients and 5 healthy volunteers and compared our PET/MRI findings between these two groups. Results: All five patients showed abnormally increased radioligand uptake on PET compared to healthy controls at various organs, including the uterus, vagina, pelvic bowel, gluteus maximus muscle, and liver. However, on MRI, only 2 patients showed abnormalities that could be potentially associated with the pain symptoms. For a subset of patients, the association of pain and the abnormally increased radioligand uptake was further validated by successful pain relief outcomes following surgery or trigger point injections to the identified abnormalities. Conclusion: In this preliminary study, sigma-1 receptor PET/MRI demonstrated potential for identifying abnormalities associated with chronic pelvic pain. Future studies will need to correlate samples with imaging findings to further validate the correlation between S1R distribution and pathologies of chronic pelvic pain. Trial Registration: The clinical trial registration date is June 2, 2018, and the registration number of the study is NCT03195270 (https://clinicaltrials.gov/ct2/show/NCT03556137).

Imaging Characteristics and Diagnostic Performance of 2-deoxy-2-[18F]fluoro-D-Glucose PET/CT for Melanoma Patients Who Demonstrate Hyperprogressive Disease When Treated with Immunotherapy.

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