Tumor and Organ Dose Estimates from ¹⁷⁷ Lu-PSMA-617 Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: Results from the RESIST-PC Phase 2 Trial

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.