Florian Rosar, Caroline Burgard, Christine Petrescu, Arne Blickle, Mark Bartholomä, Stephan Maus, Moritz B Bastian, Tilman Speicher, Andrea Schaefer-Schuler, Samer Ezziddin
{"title":"Pilot experience of [<sup>161</sup>Tb]Tb-PSMA-617 RLT in mCRPC patients after conventional PSMA RLT within a prospective registry.","authors":"Florian Rosar, Caroline Burgard, Christine Petrescu, Arne Blickle, Mark Bartholomä, Stephan Maus, Moritz B Bastian, Tilman Speicher, Andrea Schaefer-Schuler, Samer Ezziddin","doi":"10.7150/thno.115831","DOIUrl":null,"url":null,"abstract":"<p><p><i>Rationale:</i> The radionuclide <sup>161</sup>Tb is an increasingly discussed potential candidate for radioligand therapy (RLT). Through the considerable emitted amount of low-energy Auger and conversion electrons, <sup>161</sup>Tb offers physical advantages over the commonly used <sup>177</sup>Lu, resulting in higher locally absorbed doses. In this study, we present initial experience with [<sup>161</sup>Tb]Tb-PSMA-617 RLT across different clinical settings following initial PSMA RLT. <i>Methods:</i> The study involved n=18 patients with metastasized castration-resistant prostate cancer (mCRPC) participating in a prospective registry (NCT04833517) and receiving [<sup>161</sup>Tb]Tb-PSMA-617 after initial PSMA RLT with established radionuclides (<sup>177</sup>Lu, <sup>225</sup>Ac). In total 47 cycles of [<sup>161</sup>Tb]Tb-PSMA-617 RLT were administered with a median of 3 cycles (1 - 4 cycles) per patient. The mean administered activity of <sup>161</sup>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 '<i>Common Terminology Criteria for Adverse Events</i>' (CTCAE v.5.0) grading system. <i>Results:</i> In the heterogeneous cohort of patients previously experiencing insufficient response or progression post RLT with [<sup>177</sup>Lu]Lu-PSMA-617, or even after <sup>225</sup>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 [<sup>177</sup>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. <i>Conclusion:</i> These pilot results confirm <sup>161</sup>Tb as a promising radionuclide for PSMA RLT and suggest [<sup>161</sup>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.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"9019-9028"},"PeriodicalIF":13.3000,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439265/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Theranostics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7150/thno.115831","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Rationale: The radionuclide 161Tb is an increasingly discussed potential candidate for radioligand therapy (RLT). Through the considerable emitted amount of low-energy Auger and conversion electrons, 161Tb offers physical advantages over the commonly used 177Lu, resulting in higher locally absorbed doses. In this study, we present initial experience with [161Tb]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 [161Tb]Tb-PSMA-617 after initial PSMA RLT with established radionuclides (177Lu, 225Ac). In total 47 cycles of [161Tb]Tb-PSMA-617 RLT were administered with a median of 3 cycles (1 - 4 cycles) per patient. The mean administered activity of 161Tb 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 [177Lu]Lu-PSMA-617, or even after 225Ac 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 [177Lu]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 161Tb as a promising radionuclide for PSMA RLT and suggest [161Tb]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.
期刊介绍:
Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.