Personalized dosimetry assessment of [177Lu]Lu-PSMA-617 radioligand therapy in the management of metastatic castration-resistant prostate cancer

Introduction: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is revolutionizing the treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) patients. This study aimed to establish patient-specific radiation dosimetry for [Lu-177]Lu-PSMA-617 RLT in Iranian patients with mCRPC. Method: TTwelve biopsy-proven prostate cancer patients (aged 68.73 +/- 5.26 yr) underwent 6.62 +/- 0.36 GBq [Lu-177]Lu-PSMA-617 RLT. Post-therapy whole-body planar scans were acquired approximately at 4, 48, and 72 h post-administration, alongside a single SPECT/CT around 48 h using Siemens Symbia T-2 to obtain cumulated activity. An imaging protocol and dosimetry approach were designed to balance between time efficacy and accuracy in post-therapeutic dosimetry. Using accurate activity calibration, S-values were calculated by importing SPECT/CT images as the source/geometry into the Geant4 application for the tomographic emission (GATE) Monte Carlo (MC) toolkit. The Medical Internal Radiation Dose (MIRD) scheme was followed for subsequent absorbed dose (AD) calculations in organs at risk (OAR) and tumoral lesions using the dose actor and accumulated activities for precise dose estimations. Results: Using the MC approach, the mean ADs to the liver, spleen, right and left kidneys, and tumor lesions were 0.11 +/- 0.04 Gy/GBq, 0.08 +/- 0.03 Gy/GBq, 0.34 +/- 0.09 Gy/GBq, 0.34 +/- 0.10 Gy/GBq, and 0.83 +/- 0.54 Gy/GBq, respectively. Notably, tumoral lesions demonstrated significantly higher ADs, indicating enhanced uptake of radiopharmaceuticals by malignant cells. Conclusions: This study indicates that the ADs of OARs and tumoral lesions from [Lu-177]Lu-PSMA-617 RLT in patients with mCRPC are consistent with existing literature. The dosimetry findings suggest that increasing the administered activity of [Lu-177]Lu-PSMA-617 RLT is feasible and does not pose a significant risk of adverse effects on OARs, as supported by our data. However, to validate the safety and efficacy of higher doses, further clinical follow-up studies are recommended.