Abstract
Simple SummaryIn 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 [177Lu]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 [177Lu]Lu-PSMA-617 radioligand therapy.(Background) Aim of this retrospective analysis was to investigate in mCRPC patients treated with [177Lu]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 [177Lu]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 [177Lu]Lu-PSMA-targeted therapies.
Highlights
Radioligand therapies (RLT) addressing the prostate-specific membrane antigen (PSMA), have shown most promising results regarding clinical safety and efficacy in patients with progressive metastasized castration-resistance prostate cancer that are no longer responsive to treatments based on current guidelines [1,2,3,4,5]
Particular attention must be given to the poor health status of most metastasized castration-resistance prostate cancer (mCRPC) patients, which limits imaging in clinical routine more than in patients treated with DOTATATE-therapies
Calculation of the absorbed doses for organs at risk (OAR) in [177Lu]Lu-PSMA-617 therapy using simplified dosimetric schemes is feasible and easy to implement in clinical routine
Summary
Radioligand therapies (RLT) addressing the prostate-specific membrane antigen (PSMA), have shown most promising results regarding clinical safety and efficacy in patients with progressive metastasized castration-resistance prostate cancer (mCRPC) that are no longer responsive to treatments based on current guidelines [1,2,3,4,5]. In addition to legal regulations, individual assessment of doses to OAR is mandatory for a patient-specific approach in PSMA-RLT and might allow for the administration of higher cumulative activities, thereby increasing doses to the tumor and improving response to therapy significantly as recently shown by several studies [8,9,10,11,12]. This position is supported by the EANM Guideline for PSMA-targeted therapies [13]. The number of patients treated with PSMA-targeted therapies will be significantly larger [25] leading to increased utilization of imaging systems
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