¹⁷⁷Lu-PSMA-617 Single-Photon Emission Computed Tomography/Computed Tomography Dosimetry and Radiobiological Models Demonstrate Decreasing Tumor-to-Kidney Dose Ratio With Successive Cycles.

Abstract

Dosimetry studies following ¹⁷⁷Lu-PSMA-617 radioligand therapy (RLT) for metastatic castration-resistant prostate cancer have focused primarily on absorbed dose (AD). Biologically effective dose (BED) and equieffective dose in 2 Gray fractions (EQD2) further account for dose delivery rate, tissue repair rate, and radiosensitivity. Our aims were to investigate cycle-to-cycle changes in tumor and organ AD, BED, and EQD2 and tumor-to-kidney dose ratio (TKR) for the given dose metric. Serial single-photon emission computed tomography/computed tomography imaging was performed after cycle 1 or cycles 1 and 2 of ¹⁷⁷Lu-PSMA-617 RLT. BED and EQD2 were calculated using 2 sets of tumor radiobiological parameters: α/β_tumor = 3 Gy, T_rep,tumor = 0.27 hours, proposed for prostate cancer, and α/β_tumor = 10 Gy, T_rep,tumor = 1.5 hours, commonly used for other tumor types. Kidney parameters were α/β_kidney = 2.6 Gy and T_rep,kidney = 2.8 hours. TKR was compared for patients with imaging after cycles 1 and 2. The relationship between cycle 1 whole-body tumor volume (WBTV) dose metrics and change in prostate-specific antigen (PSA) level was also investigated. Ninety-one tumors were segmented in 20 patients with cycle 1 imaging; 10 also received imaging after cycle 2. Median (range) cycle 1 ADs were 17.7 (0.5-155.9) Gy to the tumor and 2.6 (0.5-10.0) Gy to the kidney. Tumor AD decreased from cycle 1 to 2, whereas organ AD remained constant. Median TKR_AD decreased from 6.6 to 3.1 while TKR_EQD2 (α/β_tumor = 10 Gy) decreased from 9.0 to 4.3. For tumors receiving higher AD, the decrease in TKR with cycle was up to 30% greater when calculated with radiobiological models than with AD. Furthermore, a significant association between early PSA response and cycle 1 WBTV dose metrics was demonstrated (Spearman ρ = 0.63, P = .005). A strong dose-response relationship was seen between cycle 1 WBTV dose metrics and a decrease in PSA. Radiobiological models can substantially impact the TKR and the cycle-to-cycle change in TKR and should be considered when investigating novel ¹⁷⁷Lu-PSMA-617 RLT dosing schemas.