Streamlined Schemes for Dosimetry of (177)Lu-Labeled PSMA Targeting Radioligands in Therapy of Prostate Cancer

SIMPLE SUMMARY: In patients with progressive metastasized castration-resistance prostate cancer PSMA radioligand therapies have shown promising results regarding clinical safety and efficacy. Dosimetry is mandatory due to legal regulations and also required for the estimation of doses to organs at risk allowing for individual tailoring of treatment in PSMA-RLT. Due to those factors and the often poor health status of patients which restricts intense dosimetric imaging protocols, there is a clear need for simplified dosimetric approaches in mCRPC patients treated with [(177)Lu]Lu-PSMA-617. In this study, we evaluated different dosimetric methodologies and found that a streamlined dosimetric approach is feasible and valid. This approach is based on single time-point imaging at 48 h p.i. in cycle 2 to 6 taking into account kinetic results of a full dosimetric scheme performed only in cycle1. These results might have a relevant impact on patients handling regarding dosimetry during [(177)Lu]Lu-PSMA-617 radioligand therapy. ABSTRACT: (Background) Aim of this retrospective analysis was to investigate in mCRPC patients treated with [(177)Lu]Lu-PSMA-617 whether the absorbed dose (AD) in organs at risk (OAR, i.e., kidneys and parotid glands) can be calculated using simplified methodologies with sufficient accuracy. For this calculation, results and kinetics of the first therapy cycle were used. (Methods) 46 patients treated with 2 to 6 cycles of [(177)Lu]Lu-PSMA-617 were included. As reference (current clinical standard) full dosimetry of the OAR based on quantitative imaging (whole body scintigraphy and quantitative SPECT/CT at 2, 24, 48 and 72 h p.i.) for every cycle was used. Alternatively, two dosimetry schemes, simplified in terms of image acquisition and dose calculation, were established, both assuming nearly unchanged kinetics of the radiopharmaceutical for subsequent cycles. (Results) In general, for both OAR the simplified methods provided results that were consistent with the dosimetric reference method, both per cycle and in terms of cumulative AD. Best results were obtained when imaging was performed at 48 h p.i. in each of the subsequent cycles. However, both simplified methods tended to underestimate the cumulative AD. (Conclusion) Simplified dosimetry schemes are feasible to tailor multi-cycle [(177)Lu]Lu-PSMA-targeted therapies.