Organ and tumor dosimetry of [161Tb]Tb-PSMA-617 radioligand therapy in patients with mCRPC

Abstract

Abstract Purpose Terbium-161 ( 161 Tb) has emerged as a promising radionuclide for radioligand therapy (RLT) due to its emission of Auger and conversion electrons, which may support therapeutic efficacy through increased local energy deposition. Despite growing research efforts aimed at the clinical potential of 161 Tb, dosimetric data, particularly for tumor lesions, remain scarce. To address this gap, we assessed tumor and organ dosimetry in mCRPC patients treated with [ 161 Tb]Tb-PSMA-617. Methods The study involved n = 15 patients with metastasized castration-resistant prostate cancer (mCRPC) participating in a registry (NCT04833517) and receiving [ 161 Tb]Tb-PSMA-617. All patients received a median of 2 (range: 1–3) cycles with mean administered activity of 6.0 ± 1.3 GBq and mean cumulative activity of 12.3 ± 4.6 GBq [ 161 Tb]Tb-PSMA-617. Hybrid dosimetry of organs at risk, including the salivary glands, the kidneys, the liver, and tumor lesions was performed analyzing whole-body planar and SPECT/CT images. Absorbed doses were estimated using OLINDA/EXM for 161 Tb. Tumor-to-organ ratios (TR) of mean tumor-absorbed doses over relevant organs at risk were calculated. Results Mean absorbed dose to kidneys, parotid glands, submandibular glands and liver was 0.70 ± 0.41 Gy/GBq, 0.40 ± 0.20 Gy/GBq, 0.36 ± 0.14 Gy/GBq and 0.13 ± 0.08 Gy/GBq, respectively. Tumor kinetics in 43 lesions demonstrated stable activity over time (mean half-life of all lesions: 44.07 h ± 15.88 h) delivering a mean overall absorbed tumor dose of 5.95 ± 3.60 Gy/GBq, the resulting TR over kidney and parotid gland were 10.55 ± 8.32 and 16.15 ± 11.85, respectively. Conclusion [ 161 Tb]Tb-PSMA-617 delivers high tumor-absorbed doses with tolerable doses to relevant organs at risk, translating into favorable tumor-to-normal-organ ratios. Dosimetry results confirm 161 Tb as a promising radionuclide for PSMA-targeted radioligand therapy in mCRPC.