Overview
Single-time-point (STP) dosimetry has emerged as a practical alternative to traditional multi-time-point approaches for radiopharmaceutical therapies. In metastatic castration-resistant prostate cancer (mCRPC) treated with Lutetium-177 labelled PSMA (177Lu-PSMA), STP dosimetry at around 48 hours post-administration can reliably estimate absorbed doses to kidneys and tumors, reducing imaging burden and streamlining clinical workflows.
Why STP Dosimetry Matters in 177Lu-PSMA Therapy
177Lu-PSMA therapy has shown meaningful survival and response benefits in mCRPC. However, post-therapeutic dosimetry aims to balance tumor dose with organ safety, particularly for the kidneys. Traditional multiple-time-point dosimetry is accurate but resource-intensive. STP dosimetry preserves essential dose information while cutting imaging sessions, enabling broader adoption in busy nuclear medicine departments.
Phantom Study and Fast SPECT Protocol
A dual-head SPECT/CT system with an MEGP collimator was optimized to acquire 177Lu images rapidly: 5 seconds per frame, 60 frames per head, about 7 minutes per bed. Reconstructions used OSEM (16 iterations, 9 subsets) with Hermes Hybrid Recon 3.0 and Gaussian modelling to reduce blur. A Jaszczak phantom calibrated with known 177Lu activity established camera-specific calibration factors per MIRD guidelines, enabling quantitative SPECT analysis and the conversion of counts to activity for dosimetry.
Clinical Application: STP Dosimetry in 177Lu-PSMA mCRPC
Eight SPECT/CT sessions across five patients treated with 177Lu-PSMA I&T (5.6–8.1 GBq; mean 6.8 GBq) were acquired at approximately 48 hours post-administration. STP voxel-based dosimetry used the Hanscheid method to estimate cumulated activity in kidneys and tumors, with doses calculated by Hermes Dosimetry Software using Monte Carlo simulations. Segmentation of kidneys and tumor targets was performed by medical physicists and verified by nuclear medicine physicians.
Kidneys
The mean kidney absorbed dose across all cycles was 2.04 Gy (SD 0.37 Gy; range 1.71–2.67 Gy), staying well below the established renal safety threshold (~23 Gy). The per-GBq kidney dose coefficient in this cohort averaged 0.31 Gy/GBq, aligning with reported ranges in the literature and underscoring renal safety for standard activity levels.
Tumors
Tumor lesions (n=25) showed substantial heterogeneity, with absorbed doses ranging from 0.98 Gy to 16.05 Gy and a mean of 5.14 Gy (SD 3.81 Gy). While most tumors received higher doses than kidneys, intrapatient and interpatient variability highlighted the need for individualized dosimetry to optimize therapeutic impact and manage expectations for response, especially when PSA declines are considered as endpoints.
<h2Clinical Implications and Future Directions
STP dosimetry with fast SPECT acquisition demonstrates clear potential to simplify post-therapeutic planning and monitoring for 177Lu-PSMA in mCRPC. The approach supports timely treatment decisions, reduces imaging burden, and can aid in tailoring therapy to each patient’s renal tolerance and tumor uptake profile. While promising, the method’s limitations include modest sample size and potential compromises in image quality with ultra-fast protocols, which warrants further validation in larger cohorts and across different imaging platforms.
Conclusion
FAST SPECT acquisitions enabling STP dosimetry for 177Lu-PSMA therapy offer a practical pathway to more efficient, patient-friendly nuclear medicine practices in mCRPC. By reliably estimating kidney and tumor absorbed doses at a single, clinically feasible time point around 48 hours post-infusion, this strategy supports safer, more effective stewardship of radiopharmaceutical therapy.
Contextual Notes
Radionuclide therapy with 177Lu-PSMA has shown efficacy in mCRPC, with pivotal trials supporting survival benefits. The move toward STP dosimetry aligns with clinical aims to balance treatment intensity with organ preservation, enabling broader access and consistent care across institutions.
