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177 Lu-prostate-specific membrane antigen (PSMA)-617 enables targeted delivery of β-particle radiation to prostate cancer. We determined its radiation dosimetry and relationships to pretherapeutic imaging and outcomes. Methods: Thirty patients with prostate cancer receiving 177 Lu-PSMA-617 within a prospective clinical trial (ACTRN12615000912583) were studied. Screening 68 Ga-PSMA-11 PET/CT demonstrated high PSMA expression in all patients. After therapy, patients underwent quantitative SPECT/CT at 4, 24, and 96 h. Pharmacokinetic uptake and clearance at a voxel level were calculated and translated into absorbed dose using voxel S values. Volumes of interest were drawn on normal tissues and tumor to assess radiation dose, and a whole-body tumor dose was defined. Correlations between PSMA PET/CT parameters, dosimetry, and biochemical and therapeutic response were analyzed to identify relationships between absorbed dose, tumor burden, and patient physiology. Results: Mean absorbed dose to kidneys, submandibular and parotid glands, liver, spleen, and bone marrow was 0.39, 0.44, 0.58, 0.1, 0.06, and 0.11 Gy/MBq, respectively. Median wholebody tumor-absorbed dose was 11.55 Gy and correlated with prostate-specific antigen (PSA) response at 12 wk. A median dose of 14.1 Gy was observed in patients achieving a PSA decline of at least 50%, versus 9.6 Gy for those achieving a PSA decline of less than 50% (P , 0.01). Of 11 patients receiving a tumor dose of less than 10 Gy, only one achieved a PSA response of at least 50%. On screening PSMA PET, whole-body tumor SUV mean correlated with mean absorbed dose (r 5 0.62), and SUV max of the parotids correlated with absorbed dose (r 5 0.67). There was an inverse correlation between tumor volume and mean dose to the parotids (r 5 −0.41) and kidneys (r 5 −0.43). The mean parotid dose was also reduced with increasing body mass (r 5 −0.41) and body surface area (r 5 −0.37). Conclusion: 177 Lu-PSMA-617 delivers high absorbed doses to tumor, with a significant correlation between whole-body tumor dose and PSA response. Patients receiving less than 10 Gy were unlikely to achieve a fall in PSA of at least 50%. Significant correlations between aspects of screening 68 Ga-PET/CT and tumor and normal tissue dose were observed, providing a rationale for patient-specific dosing. Reduced salivary and kidney doses were observed in patients with a higher tumor burden. The parotid dose also reduced with increasing body mass and body surface area.

Lu-PSMA-617 is a radioligand with high affinity for prostate-specific membrane antigen (PSMA), enabling targeted β-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castration-resistant prostate cancer. We now report their longer-term outcomes, including a 20-patient extension cohort and outcomes of subsequent systemic treatments after completion of trial therapy. Methods: Fifty patients with PSMA-avid metastatic castration-resistant prostate cancer who had progressed after standard therapies received up to 4 cycles of 177 Lu-PSMA every 6 wk. Endpoints included prostate-specific antigen (PSA) response (Prostate Cancer Working Group 2), toxicity (Common Terminology Criteria for Adverse Events, version 4.03), imaging response, patient-reported health-related quality of life, progression-free survival, and overall survival. We also describe, as a novel finding, outcomes of men who subsequently progressed and had further systemic therapies, including 177 Lu-PSMA. Results: Seventy-five men were screened to identify 50 patients eligible for treatment. Adverse prognostic features of the cohort included short median PSA doubling time (2.3 mo) and extensive prior treatment, including prior docetaxel (84%), cabazitaxel (48%), and abiraterone or enzalutamide (92%). The mean administered radioactivity was 7.5 GBq/cycle. A PSA decline of at least 50% was achieved in 32 of 50 patients (64%; 95% confidence interval [CI], 50%-77%), including 22 patients (44%; 95% CI, 30%-59%) with at least an 80% decrease. Of 27 patients with measurable soft-tissue disease, 15 (56%) achieved an objective response by RECIST 1.1. The most common toxicities attributed to 177 Lu-PSMA were self-limiting G1-G2 dry mouth (66%), transient G1-G2 nausea (48%), G3-G4 thrombocytopenia (10%), and G3 anemia (10%). Brief Pain Inventory severity and interference scores decreased at all time points, including at the 3-mo follow-up, with a decrease of −1.2 (95% CI, −0.5 to −1.9; P 5 0.001) and −1.0 (95% CI, −0.2 to −0.18; P 5 0.013), respectively. At a median follow-up of 31.4 mo, median overall survival was 13.3 mo (95% CI, 10.5-18.7 mo), with a significantly longer survival of 18.4 mo (95% CI, 13.8-23.8 mo) in patients achieving a PSA decline of at least 50%. At progression after prior response, further 177 Lu-PSMA was administered to 15 (30%) patients (median of 2 cycles commencing 359 d from enrollment), with a PSA decline of at least 50% in 11 patients (73%). Four of 21 patients (19%) receiving other systemic therapies on progression experienced a PSA decline of at least 50%. There were no unexpected adverse events with 177 Lu-PSMA retreatment. Conclusion: This expanded 50-patient cohort of men with extensive prior therapy confirms our earlier report of high response rates, low toxicity, and improved quality of life with 177 Lu-PSMA radioligand therapy. On progression, rechallenge 177 Lu-PSMA demonstrated higher response rates than other systemic t...

GaTate PET/CT imaging provides additional diagnostic information in a high proportion of patients with consequent high management impact. GaTate PET/CT could replace (1)In-111 octreotide scintigraphy at centres where it is available given its superior accuracy, faster acquisition and lower radiation exposure. Rapid implementation could be achieved by allowing substitutional funding in the Medicare Benefit Schedule.

BackgroundPheochromocytomas (PCC) and paragangliomas (PGL) are neuroendocrine tumours arising from pluripotent neural crest stem cells and are associated with neurons of the autonomic nervous system. PCCs/PGLs are often hereditary and multifocal, and their biologic behaviour and metabolic activity vary making imaging of these tumours challenging. The imaging gold standard has been I-123 MIBG complemented by CT or MRI. PGLs being neuroendocrine tumours express somatostatin receptors enabling imaging with Ga-68 DOTA-coupled peptides such as DOTATATE. Imaging with F-18 FDG also provides additional information regarding metabolic activity and biologic aggressiveness of these tumours, or, in some situations, reflecting metabolic reprogramming of these tumours. We report our experience using both Ga-68 DOTATATE and F-18 FDG PET/CT imaging in patients with PGLs and PCCs.MethodsThis was a retrospective review of 23 patients with proven PGL/PCC who underwent both DOTATATE and FDG PET/CT. Seven patients also had I-123 MIBG SPECT/CT and 1 patient had I-124 MIBG PET/CT. Lesional intensity and patterns of uptake were analysed.ResultsDOTATATE and FDG were positive at most sites of disease (96.2 % vs 91.4 %), although uptake intensity was significantly higher on DOTATATE with a median SUV of 21 compared to 12.5 for FDG (p < 0.001). SUVmax on F-18 FDG was significantly higher (p < 0.001) in clinically aggressive cases. I-123/I-124 MIBG detected fewer lesions (30.4 %).ConclusionOverall, Ga-68 DOTATATE PET/CT detected similar number but has significantly greater lesion-to-background contrast compared to F-18 FDG PET/CT. Combined with high specificity, patient convenience and relatively low cost, DOTATATE PET/CT should be considered the ideal first line investigation for imaging PGL/PCC. Depending on DOTATATE findings and the clinical question, FDG and MIBG remain useful and, in selected cases, may provide more accurate staging, disease characterisation and guide treatment choices.