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

Abstract

(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.

Toward Single-Time-Point Image-Based Dosimetry of177Lu-PSMA-617 Therapy

“…time point is more favorable if smaller range of variations in PD against TIA ref are preferred (Figure 3A, left, and Figure 4A, middle). Our results agree with those reported by Kurth et al (26) who applied the STP prior approach for cycles 2 to 6, and found differences in AD of ±6% for kidneys and ±10% for parotid glands when using a single SPECT at 48h p.i. of 177 Lu-PSMA-617 compared to MTP.…”

“…In this work, we aimed at comparing STP against MTP image-based dosimetry methods, which could increase adoption in the clinical environment. STP dosimetry methods have been studied predominantly for 177 Lu-DOTATATE therapy (13,(21)(22)(23), but also for 177 Lu-PSMA therapy (24)(25)(26). Three different approaches for STP dosimetry have been proposed: 1) using population based mean T 1/2 eff (27),…”

“…2) using prior information from the first therapy cycle for subsequent cycles (26), and 3) using the formula by Hänscheid et al (13). The first approach has been suggested to be valid for the calculation of kidneys ADs in 177 Lu-DOTATATE and 90 Y DOTATOC therapies (22,27).…”

Optimization of the radiation dosimetry protocol in Lutetium-177-PSMA therapy: toward clinical implementation

“…Since we previously showed that for this patient cohort, tracer uptake kinetics in organs are comparable to those in metastasized castrate-resistant prostate cancer (mCRPC) patients [ 14 ], we postulate that the results of this study could be translated to dosimetry in mCRPC patients as well. This is also supported by recent findings of comparable studies in this patient population [ 30 – 33 ]. For lesion dosimetry, a two-time point protocol is proposed; so, no general kinetics apart from a single compartment distribution are assumed.…”

Towards Routine Clinical Use of Dosimetry in [177Lu]Lu-PSMA Prostate Cancer Radionuclide Therapy: Current Efforts and Future Perspectives

“…Various studies have demonstrated the use of simplified dosimetry calculation methodologies for potential clinical adaptation. Recent work reported on two simplified [ 177 Lu]Lu-PSMA-617 dosimetry schemes for organs at risk, whereby one method simplified image acquisition and the other, dose calculation [60]. The simplified schemes were found to be feasible and showed potential for simplification in future works, and were both consistent with their reference method for cumulative absorbed dose.…”