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

Abstract

Terbium-161 (¹⁶¹Tb) 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 ¹⁶¹Tb, dosimetric data, particularly for tumor lesions, remain scarce. To address this gap, we assessed tumor and organ dosimetry in mCRPC patients treated with [¹⁶¹Tb]Tb-PSMA-617. The study involved n = 15 patients with metastasized castration-resistant prostate cancer (mCRPC) participating in a registry (NCT04833517) and receiving [¹⁶¹Tb]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 [¹⁶¹Tb]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 ¹⁶¹Tb. Tumor-to-organ ratios (TR) of mean tumor-absorbed doses over relevant organs at risk were calculated. 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. [¹⁶¹Tb]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 ¹⁶¹Tb as a promising radionuclide for PSMA-targeted radioligand therapy in mCRPC.