Objectives. In patients with prostate cancer (PC) receiving prostate-specific membrane antigen- (PSMA-) targeted radioligand therapy (RLT), higher baseline standardized uptake values (SUVs) are linked to improved outcome. Thus, readers deciding on RLT must have certainty on the repeatability of PSMA uptake metrics. As such, we aimed to evaluate the test-retest repeatability of lesion uptake in a large cohort of patients imaged with 18F-DCFPyL. Methods. In this prospective, IRB-approved trial (NCT03793543), 21 patients with history of histologically proven PC underwent two 18F-DCFPyL PET/CTs within 7 days (mean 3.7, range 1 to 7 days). Lesions in the bone, lymph nodes (LN), and other organs were manually segmented on both scans, and uptake parameters were assessed (maximum (SUVmax) and mean (SUVmean) SUVs), PSMA-tumor volume (PSMA-TV), and total lesion PSMA (TL-PSMA, defined as PSMA − TV × SU V mean )). Repeatability was determined using Pearson’s correlations, within-subject coefficient of variation (wCOV), and Bland-Altman analysis. Results. In total, 230 pairs of lesions (177 bone, 38 LN, and 15 other) were delineated, demonstrating a wide range of SUVmax (1.5–80.5) and SUVmean (1.4–24.8). Including all sites of suspected disease, SUVs had a strong interscan correlation ( R 2 ≥ 0.99 ), with high repeatability for SUVmean and SUVmax (wCOV, 7.3% and 12.1%, respectively). High SUVs showed significantly improved wCOV relative to lower SUVs ( P < 0.0001 ), indicating that high SUVs are more repeatable, relative to the magnitude of the underlying SUV. Repeatability for PSMA-TV and TL-PSMA, however, was low ( wCOV ≥ 23.5 %). Across all metrics for LN and bone lesions, interscan correlation was again strong ( R 2 ≥ 0.98 ). Moreover, LN-based SUVmean also achieved the best wCOV (3.8%), which was significantly reduced when compared to osseous lesions (7.8%, P < 0.0001 ). This was also noted for SUVmax (wCOV, LN 8.8% vs. bone 12.0%, P < 0.03 ). On a compartment-based level, wCOVs for volumetric features were ≥22.8%, demonstrating no significant differences between LN and bone lesions (PSMA-TV, P =0.63; TL-PSMA, P =0.9). Findings on an entire tumor burden level were also corroborated in a hottest lesion analysis investigating the SUVmax of the most intense lesion per patient ( R 2 , 0.99; wCOV, 11.2%). Conclusion. In this prospective test-retest setting, SUV parameters demonstrated high repeatability, in particular in LNs, while volumetric parameters demonstrated low repeatability. Further, the large number of lesions and wide distribution of SUVs included in this analysis allowed for the demonstration of a dependence of repeatability on SUV, with higher SUVs having more robust repeatability.

Neuroendocrine tumors (NETs) show low but increasing incidence and originate in multiple organs, including the pancreas, midgut, caecum, rectum, appendix, colon, and lungs. Due to their stunning genetic, histological, and clinical variability, diagnosis and treatment of NETs are challenging. In addition, low incidence and high variability hamper the implementation of high evidence trials. Therefore, guidelines do not cover the complexity of NETs and, frequently, treatment decisions are taken by interdisciplinary tumor conferences at comprehensive cancer centers. Treatment aims are (i) control of tumor growth, (ii) symptom control, as well as (iii) the improvement of progression-free survival (PFS) and overall survival (OS). Here, we discuss high evidence trials facilitating the achievement of these treatment aims. The majority of the evidence exists for treatment with somatostatin analogue, everolimus, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE, sunitinib, and telotristat. Among those, PRRT is the only treatment option that has the potential to control symptoms, stop tumor growth, and to improve PFS and OS. In contrast, only a low level of evidence exists for treatment with cytotoxic drugs such as streptozotocin and doxorubicine. Finally, we discuss novel treatment options by a combination of cytotoxic drugs, 177Lu-DOTATATE, and tyrosine kinase inhibitors to be tested in randomized prospective trials in the future. In addition, the application of innovative isotopes, such as 225Ac, for PRRT is discussed.

Patient history, diagnosis and therapy ▶ Fig. 1 Gallium-68-PSMA PET/CT before radionuclide therapy with Lutetium-177-PSMA: intense activity accumulation in a metastasis of prostate cancer the left breast.

Objectives We evaluated 18F‐DCFPyL test–retest repeatability of uptake in normal organs. Methods Twenty‐two prostate cancer (PC) patients underwent two 18F‐DCFPyL PET scans within 7 days within a prospective clinical trial (NCT03793543). In both PET scans, uptake in normal organs (kidneys, spleen, liver, and salivary and lacrimal glands) was quantified. Repeatability was determined by using within‐subject coefficient of variation (wCOV), with lower values indicating improved repeatability. Results For SUVmean, repeatability was high for kidneys, spleen, liver, and parotid glands (wCOV, range: 9.0%–14.3%) and lower for lacrimal (23.9%) and submandibular glands (12.4%). For SUVmax, however, the lacrimal (14.4%) and submandibular glands (6.9%) achieved higher repeatability, while for large organs (kidneys, liver, spleen, and parotid glands), repeatability was low (range: 14.1%–45.2%). Conclusion We found acceptable repeatability of uptake on 18F‐DCFPyL PET for normal organs, in particular for SUVmean in the liver or parotid glands. This may have implications for both PSMA‐targeted imaging and treatment, as patient selection for radioligand therapy and standardized frameworks for scan interpretation (PROMISE, E‐PSMA) rely on uptake in those reference organs.

Objectives: PET-based radiomic metrics are increasingly utilized as predictive image biomarkers. However, the repeatability of radiomic features on PET has not been assessed in a test-retest setting. The prostate-specific membrane antigen-targeted compound 18 F-DCFPyL is a high-affinity, high-contrast PET agent that we utilized in a test-retest cohort of men with metastatic prostate cancer (PC).Methods: Data of 21 patients enrolled in a prospective clinical trial with histologically proven PC underwent two 18 F-DCFPyL PET scans within 7 days, using identical acquisition and reconstruction parameters. Sites of disease were segmented and a set of 29 different radiomic parameters were assessed on both scans. We determined repeatability of quantification by using Pearson's correlations, within-subject coefficient of variation (wCOV), and Bland-Altman analysis.

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