Overview
Single time-point (STP) dosimetry is gaining traction in the management of metastatic castration-resistant prostate cancer (mCRPC) treated with Lutetium-177 labeled PSMA (177Lu-PSMA). This approach aims to estimate absorbed radiation doses with a single post-therapy imaging session, typically around 48 hours, reducing imaging burden and resource use compared with traditional multi-time-point (MTP) dosimetry. Here we review a phantom-validated clinical study that evaluates fast SPECT acquisitions for STP dosimetry in 177Lu-PSMA treated patients and discusses its implications for routine nuclear medicine practice.
Rationale for STP Dosimetry at 48 Hours
Kidneys are the critical organ at risk due to radiotracer excretion, and ensuring their dose remains within safe limits is essential. Tumour-absorbed doses are equally important, as higher tumour uptake generally correlates with therapeutic efficacy. STP dosimetry at about 48 hours post-administration has been proposed as the optimal imaging time to capture sufficient radiopharmaceutical distribution for both organs and lesions, enabling practical, voxel-based dose estimation while minimizing patient burden.
Methods: Phantom and Clinical Setup
The study used a GE Discovery 870 DR dual-head SPECT/CT with an MEGP collimator. A Jaszczak phantom with known 177Lu activity enabled camera-specific calibration following MIRD Pamphlet No. 26. Fast SPECT acquisitions were implemented at 5 seconds per frame across 60 frames per head (7 minutes per bed). Quantitative reconstruction used OSEM (16 iterations, 9 subsets) with a 128×128 matrix and Gaussian collimator–detector blur modeling. Attenuation correction CT was performed with a low-dose protocol.
Clinical imaging comprised eight treatment cycles in five patients, each receiving 177Lu-PSMA I&T (5.6–8.1 GBq; mean 6.8 GBq). Scans were conducted around 48 hours post-infusion. STP voxel-based dosimetry of kidneys and tumours employed the Hanscheid method in Hermes Dosimetry Software to estimate cumulated activity and subsequently absorbed dose.
Dosimetry and Key Findings
Kidney doses were consistent across patients, with a mean of 2.04 Gy (SD 0.37 Gy, range 1.71–2.67 Gy). This remained well below the accepted renal threshold of ~23 Gy, supporting the safety of administered activities within this cohort (mean dose coefficient ~0.31 Gy/GBq).
Tumour doses varied widely (n=25 lesions), from 0.98 Gy to 16.05 Gy, with a mean of 5.14 Gy (SD 3.81 Gy). Most tumours received higher absorbed doses than kidneys, indicating targeted activity uptake and potential for meaningful therapeutic effect. Inter- and intra-patient heterogeneity highlighted the need for individualized dosimetry to interpret treatment response and plan subsequent cycles.
Across five patients and eight cycles, organ and lesion dosimetry demonstrated the feasibility of STP approaches. In particular, intrathoracic and skeletal metastases showed dose variability consistent with biological differences, lesion size, location, and PSMA expression. Overall, the data align with the concept that higher tumour-absorbed doses correlate with PSA responses and lesion control observed in broader 177Lu-PSMA trials, while kidney doses remained within safe limits.
Clinical Implications and Future Directions
The adoption of fast SPECT acquisitions coupled with STP dosimetry offers a practical path to reduce imaging and workflow burden in nuclear medicine while maintaining patient safety through organ dosimetry. The results support extending such workflow to routine care, with careful attention to image quality in small or low-uptake lesions and ongoing renal function monitoring.
Limitations include a small sample size and potential trade-offs between acquisition speed and image resolution. Future work should explore larger, prospective cohorts, optimization of reconstruction parameters for low-count data, and integration with adaptive treatment planning that uses early post-therapy dosimetry to tailor subsequent cycles or consider alternative radiopharmaceuticals for refractory disease.
Conclusion
Fast SPECT acquisitions enable reliable STP dosimetry for 177Lu-PSMA in mCRPC, providing actionable absorbed dose information for kidneys and tumours at ~48 hours post-administration. This approach promises to reduce imaging burden while preserving dosimetric accuracy, supporting safer, more efficient, and potentially more effective radionuclide therapy.
