Abstract
Rationale: The radionuclide (161)Tb is an increasingly discussed potential candidate for radioligand therapy (RLT). Through the considerable emitted amount of low-energy Auger and conversion electrons, (161)Tb offers physical advantages over the commonly used (177)Lu, resulting in higher locally absorbed doses. In this study, we present initial experience with [(161)Tb]Tb-PSMA-617 RLT across different clinical settings following initial PSMA RLT. Methods: The study involved n=18 patients with metastasized castration-resistant prostate cancer (mCRPC) participating in a prospective registry (NCT04833517) and receiving [(161)Tb]Tb-PSMA-617 after initial PSMA RLT with established radionuclides ((177)Lu, (225)Ac). In total 47 cycles of [(161)Tb]Tb-PSMA-617 RLT were administered with a median of 3 cycles (1 - 4 cycles) per patient. The mean administered activity of (161)Tb per cycle was 6.2 ± 0.8 GBq, the mean cumulative activity was 16.1 ± 4.9 GBq. Outcome was evaluated by biochemical and molecular imaging response, progression-free survival (PFS), and overall survival (OS). Adverse events were assessed by 'Common Terminology Criteria for Adverse Events' (CTCAE v.5.0) grading system. Results: In the heterogeneous cohort of patients previously experiencing insufficient response or progression post RLT with [(177)Lu]Lu-PSMA-617, or even after (225)Ac augmentation, biochemical and molecular imaging response rates were 38.9% and 44.4%, median PFS and OS 3.5 and 11.3 months, respectively. The best response and outcome were observed in patients who initially responded to [(177)Lu]Lu-PSMA-617 RLT. The majority of all post therapeutically recorded adverse events were mild or moderate (CTCAE °1 or °2); higher grades (CTCAE °3 or °4) were rarely observed (2 cases of thrombocytopenia, 4 cases of anemia and 4 cases of renal impairment). No treatment discontinuation due to therapy related adverse events was recorded. Conclusion: These pilot results confirm (161)Tb as a promising radionuclide for PSMA RLT and suggest [(161)Tb]Tb-PSMA-617 as a potential effective and safe treatment option even in the advanced mCRPC setting after multi-line systemic therapies including standard PSMA RLT. Larger studies are warranted to confirm and extend this initial experience and clinical trials even in earlier CRPC settings appear promising based on our initial impression of this radionuclide-based novelty in PSMA RLT.