Tumor dosimetry of [¹⁷⁷Lu]Lu-PSMA-617 for the treatment of metastatic castration-resistant prostate cancer: Results from the VISION trial sub-study.

5046 Background: In VISION, lutetium ( 177 Lu) vipivotide tetraxetan ([ 177 Lu]Lu-PSMA-617; 177 Lu-PSMA-617) plus protocol-permitted standard of care (SoC) significantly improved overall survival and radiographic progression-free survival compared with SoC alone, in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer. In a VISION dosimetry sub-study, 177 Lu-PSMA-617 had a good safety profile with low radiotoxicity in at-risk organs. Here, we estimated the dosimetry of tumors after administration of 177 Lu-PSMA-617. Methods: The VISION sub-study was performed in a separate cohort of 29 non-randomized participants at four sites in Germany. Eligible patients received 177 Lu-PSMA-617 (7.4 GBq every 6 weeks, ≤ 6 cycles) plus SoC. Patients underwent single-photon emission computed tomography/computed tomography (SPECT/CT) scans at approximately 2, 24, 48 and 168 hours after the first administration of 177 Lu-PSMA-617 (Cycle 1). Up to five tumors in each patient were selected according to tumor size and relative activity uptake. Tumor delineation, volume and morphology were determined using positron emission tomography (PET)/CT images. Kinetic (time-activity) data was determined using SPECT images and the application of phantom derived recovery coefficients. Tumor dosimetry was estimated using the standard Medical Internal Radiation Dose/Radiation Dose Assessment Resource (MIRD/RADAR) method for internal dosimetry. S-values were determined using CT-derived tumor volumes and tissue type as input to the Internal Dose Assessed by Computer (IDAC-Dose) 2.1 program. Tumor dosimetry estimates were reported as absorbed dose per unit activity (Gy/GBq) and cumulative estimated absorbed dose (Gy) over all 6 cycles (44.4 GBq cumulative activity). Results: In total, 104 tumors were analyzed after administration of 177 Lu-PSMA-617 in Cycle 1. Tumor sites included bone (n = 84), lymphatic tissue (n = 18), lung tissue (n = 1) and soft tissue (n = 1). Mean tumor mass by site was 14.6 (standard deviation [SD], 29.8; range, 0.49–224) g for bone and 12.5 (15.9; 0.68–60.7) g for lymphatic tissue. The mean radiation-absorbed dose for all tumors was 6.5 (SD, 8.4; range, 0.13–55) Gy/GBq, and the median absorbed dose was 4.4 Gy/GBq. The mean radiation-absorbed dose by tumor site was 5.4 (SD, 6.0; range, 0.13–45) Gy/GBq for bone and 9.7 (12; 0.99–55) Gy/GBq for lymphatic tissue. The 6-cycle cumulative estimated absorbed dose for all tumors was 287 (SD, 373; range, 5.7–2432) Gy. The 6-cycle cumulative estimated absorbed dose by tumor site was 240 (SD, 268; range, 5.7–2010) Gy for bone and 429 (549; 44–2432) Gy for lymphatic tissue. Conclusions: Tumor dosimetry estimates after administration of 177 Lu-PSMA-617 in the VISION sub-study patient population were consistent with previously published estimates. Clinical trial information: NCT03511664 .