Validation of Manual In-House Synthesis, Imaging, Biodistribution, and Dosimetry of Tb-161 PSMA-617 for mCRPC Patients in a Tertiary Health Care Center: A Proof-of-Concept Study

Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a therapeutic challenge, particularly in patients with suboptimal response to 177 Lu PSMA-617. Terbium-161 (Tb-161), with its emission of β-particles and high-LET Auger/conversion electrons, offers potential advantages in targeting micrometastases. However, clinical validation, especially in resource-limited settings, remains limited. Materials and Methods: This single-center, proof-of-concept study was conducted at the Department of Nuclear Medicine, FMRI, Gurgaon. Manual in-house radiolabeling of Tb-161 with PSMA-617 was performed. The samples were withdrawn for quality control analyses. Five mCRPC patients were administered Tb-161 PSMA-617. Post-therapy planar and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging was conducted to assess biodistribution and dosimetric analysis. Results: Radiolabeling Tb-161 with PSMA-617 was more than 95% efficient with 55 min of heating at 95°C. The radiochemical purity was >98% for all the runs ( n = 5). The sample was found to be sterile with no gel formation seen after 15 d for all the batches. Post-therapy imaging demonstrated favorable biodistribution and high tumor uptake. Dosimetric analysis revealed absorbed doses comparable or superior to historical 177 Lu-PSMA-617 data. No acute adverse events or safety concerns were observed post administration. Conclusions: This study successfully demonstrates the feasibility of manual in-house synthesis and clinical application of Tb-161 PSMA-617 in an Indian tertiary care setting. The favorable synthesis, imaging, biodistribution, and dosimetric profile support its potential as a next-generation theranostic agent for mCRPC. These findings warrant further validation through larger, controlled clinical trials.