Abstract
This is a dosimetry analysis of the prospective randomized phase 2 trial RESIST-PC which evaluated the efficacy and safety of 2 injected activity regimens of [177Lu]Lu-PSMA-617 in patients with progressive metastatic castration-resistant prostate cancer. Methods: This biinstitutional study randomized patients with metastatic castration-resistant prostate cancer to receive either 6.0 or 7.4 GBq of [177Lu]Lu-PSMA-617 per cycle for up to 4 cycles (1:1 randomization). The γ-images were obtained at the first cycle using a hybrid protocol (planar + SPECT). Whole-body planar scintigraphy images were acquired at 4, 24, 48, and 72 h (optionally at 168 h), and a quantitative SPECT/CT was performed at 24 h postinjection. Absorbed doses (ADs) were calculated for the kidneys, salivary glands, liver, and tumors. Planar time-activity curves were derived on a per-region basis from counts in the serial scans, with exponential curve fit selection based on Akaike information criterion. Quantitative SPECT data per region were scaled by the planar time-activity data and then convolved with a voxel-S value dose kernel to yield AD estimates. No partial volume corrections were applied. Adverse events and efficacy data were correlated to the calculated AD. Results: A total of 48 of 64 patients (16 treated with 6.0 GBq vs. 32 in the 7.4-GBq arm) had complete imaging datasets and were analyzed. The mean kidney, submandibular, parotid, and liver ADs were 0.29 ± 0.11, 0.23 ± 0.18, 0.26 ± 0.15, and 0.11 ± 0.09 Gy/GBq, respectively. There was no significant difference in organ or tumor ADs between arms. In total, 358 lesions were included in the analysis (median, 7/patient [range, 0-18/patient]). The mean AD to bone lesions (n = 304) was 1.90 ± 1.83 and 1.64 ± 1.77 Gy/GBq for the 6.0-GBq (n = 121) and 7.4-GBq (n = 183) groups, respectively. For lymph node lesions (n = 35), mean ADs were 5.61 ± 3.93 Gy/GBq (n = 22) and 1.79 ± 1.96 Gy/GBq (n = 13) for the 6.0- and 7.4-GBq groups, respectively. Only the 7.4-GBq cohort presented liver lesions; mean AD was 1.59 ± 1.45 Gy/GBq (n = 19). A statistically significant inverse correlation was observed between prostate-specific antigen response and tumor AD (ρ = -0.404, P = 0.006). Conclusion: In the RESIST-PC prospective phase 2 trial, dosimetry analyses using a hybrid imaging protocol revealed organ ADs within tolerable ranges, and tumor ADs varied widely on the inter- and intrapatient level regardless of injected activity.