Alexander Gäble, Alexander Dierks, Andreas Rinscheid, Marianne Patt, Georgine Wienand, Christian H Pfob, Malte Kircher, Kazuhito Fukushima, Ana Antić Nikolić, Johanna S Enke, Tilman Janzen, Julie Steinestel, Hildegard Kempter, Martin Trepel, Dorothea Weckermann, Constantin Lapa, Ralph A Bundschuh
{"title":"使用[177Lu]Lu-rhPSMA-10.1对[177Lu]Lu-PSMA-I&T原发性或获得性耐药性患者进行抢救性治疗的经验。","authors":"Alexander Gäble, Alexander Dierks, Andreas Rinscheid, Marianne Patt, Georgine Wienand, Christian H Pfob, Malte Kircher, Kazuhito Fukushima, Ana Antić Nikolić, Johanna S Enke, Tilman Janzen, Julie Steinestel, Hildegard Kempter, Martin Trepel, Dorothea Weckermann, Constantin Lapa, Ralph A Bundschuh","doi":"10.1007/s00259-024-06959-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Radioligand therapy is an increasingly important option for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Radiohybrid ligands targeting prostate-specific membrane antigen (PSMA) are a novel group of theranostic radioligand therapy agents for which higher tumour absorbed radiation doses have been demonstrated compared to established PSMA ligands. Here, we report data from ten patients who were treated within a compassionate use program with the radiohybrid PSMA-ligand [<sup>177</sup>Lu]Lu-rhPSMA-10.1 after experiencing disease progression under treatment with [<sup>177</sup>Lu]Lu-PSMA-I&T.</p><p><strong>Methods: </strong>Ten patients with advanced PSMA-positive prostate cancer who showed progression under treatment with [<sup>177</sup>Lu]Lu-PSMA-I&T received up to three cycles of rescue therapy with [<sup>177</sup>Lu]Lu-rhPSMA-10.1 (7.4-8.1 GBq per cycle). Efficacy (PSA response according to PCWG3 and RECIP) and overall survival were evaluated. Adverse events were recorded from first application.</p><p><strong>Results: </strong>Despite progression with [<sup>177</sup>Lu]Lu-PSMA-I&T, after the first cycle of [<sup>177</sup>Lu]Lu-rhPSMA-10.1 rescue therapy, five patients (50%) showed a decrease in serum PSA level. In imaging, three of the ten patients (30%) showed a partial radiologic response. Four of the five patients with a decrease of serum PSA under [<sup>177</sup>Lu]Lu-rhPSMA-10.1 had initially responded to treatment with [<sup>177</sup>Lu]Lu-PSMA-I&T but had become resistant. However, the remaining patient had shown continuous disease progression during [<sup>177</sup>Lu]Lu-PSMA-I&T therapy but showed an immediate response to [<sup>177</sup>Lu]Lu-rhPSMA-10.1. The additional treatment with [<sup>177</sup>Lu]Lu-rhPSMA-10.1 was generally well tolerated by all patients.</p><p><strong>Conclusions: </strong>Patients showing tumour progression while receiving [<sup>177</sup>Lu]Lu-PSMA-I&T radioligand therapy may benefit from rescue therapy with the novel radiohybrid PSMA ligand, [<sup>177</sup>Lu]Lu-rhPSMA-10.1. Higher tumour absorbed radiation doses with [<sup>177</sup>Lu]Lu-rhPSMA-10.1 may overcome primary and acquired radiation resistance.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Experience of rescue therapy with [<sup>177</sup>Lu]Lu-rhPSMA-10.1 in patients with primary or acquired resistance to [<sup>177</sup>Lu]Lu-PSMA-I&T.\",\"authors\":\"Alexander Gäble, Alexander Dierks, Andreas Rinscheid, Marianne Patt, Georgine Wienand, Christian H Pfob, Malte Kircher, Kazuhito Fukushima, Ana Antić Nikolić, Johanna S Enke, Tilman Janzen, Julie Steinestel, Hildegard Kempter, Martin Trepel, Dorothea Weckermann, Constantin Lapa, Ralph A Bundschuh\",\"doi\":\"10.1007/s00259-024-06959-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Radioligand therapy is an increasingly important option for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Radiohybrid ligands targeting prostate-specific membrane antigen (PSMA) are a novel group of theranostic radioligand therapy agents for which higher tumour absorbed radiation doses have been demonstrated compared to established PSMA ligands. Here, we report data from ten patients who were treated within a compassionate use program with the radiohybrid PSMA-ligand [<sup>177</sup>Lu]Lu-rhPSMA-10.1 after experiencing disease progression under treatment with [<sup>177</sup>Lu]Lu-PSMA-I&T.</p><p><strong>Methods: </strong>Ten patients with advanced PSMA-positive prostate cancer who showed progression under treatment with [<sup>177</sup>Lu]Lu-PSMA-I&T received up to three cycles of rescue therapy with [<sup>177</sup>Lu]Lu-rhPSMA-10.1 (7.4-8.1 GBq per cycle). Efficacy (PSA response according to PCWG3 and RECIP) and overall survival were evaluated. Adverse events were recorded from first application.</p><p><strong>Results: </strong>Despite progression with [<sup>177</sup>Lu]Lu-PSMA-I&T, after the first cycle of [<sup>177</sup>Lu]Lu-rhPSMA-10.1 rescue therapy, five patients (50%) showed a decrease in serum PSA level. In imaging, three of the ten patients (30%) showed a partial radiologic response. Four of the five patients with a decrease of serum PSA under [<sup>177</sup>Lu]Lu-rhPSMA-10.1 had initially responded to treatment with [<sup>177</sup>Lu]Lu-PSMA-I&T but had become resistant. However, the remaining patient had shown continuous disease progression during [<sup>177</sup>Lu]Lu-PSMA-I&T therapy but showed an immediate response to [<sup>177</sup>Lu]Lu-rhPSMA-10.1. The additional treatment with [<sup>177</sup>Lu]Lu-rhPSMA-10.1 was generally well tolerated by all patients.</p><p><strong>Conclusions: </strong>Patients showing tumour progression while receiving [<sup>177</sup>Lu]Lu-PSMA-I&T radioligand therapy may benefit from rescue therapy with the novel radiohybrid PSMA ligand, [<sup>177</sup>Lu]Lu-rhPSMA-10.1. Higher tumour absorbed radiation doses with [<sup>177</sup>Lu]Lu-rhPSMA-10.1 may overcome primary and acquired radiation resistance.</p>\",\"PeriodicalId\":11909,\"journal\":{\"name\":\"European Journal of Nuclear Medicine and Molecular Imaging\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.6000,\"publicationDate\":\"2024-11-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Nuclear Medicine and Molecular Imaging\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00259-024-06959-5\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Nuclear Medicine and Molecular Imaging","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00259-024-06959-5","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Experience of rescue therapy with [177Lu]Lu-rhPSMA-10.1 in patients with primary or acquired resistance to [177Lu]Lu-PSMA-I&T.
Purpose: Radioligand therapy is an increasingly important option for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Radiohybrid ligands targeting prostate-specific membrane antigen (PSMA) are a novel group of theranostic radioligand therapy agents for which higher tumour absorbed radiation doses have been demonstrated compared to established PSMA ligands. Here, we report data from ten patients who were treated within a compassionate use program with the radiohybrid PSMA-ligand [177Lu]Lu-rhPSMA-10.1 after experiencing disease progression under treatment with [177Lu]Lu-PSMA-I&T.
Methods: Ten patients with advanced PSMA-positive prostate cancer who showed progression under treatment with [177Lu]Lu-PSMA-I&T received up to three cycles of rescue therapy with [177Lu]Lu-rhPSMA-10.1 (7.4-8.1 GBq per cycle). Efficacy (PSA response according to PCWG3 and RECIP) and overall survival were evaluated. Adverse events were recorded from first application.
Results: Despite progression with [177Lu]Lu-PSMA-I&T, after the first cycle of [177Lu]Lu-rhPSMA-10.1 rescue therapy, five patients (50%) showed a decrease in serum PSA level. In imaging, three of the ten patients (30%) showed a partial radiologic response. Four of the five patients with a decrease of serum PSA under [177Lu]Lu-rhPSMA-10.1 had initially responded to treatment with [177Lu]Lu-PSMA-I&T but had become resistant. However, the remaining patient had shown continuous disease progression during [177Lu]Lu-PSMA-I&T therapy but showed an immediate response to [177Lu]Lu-rhPSMA-10.1. The additional treatment with [177Lu]Lu-rhPSMA-10.1 was generally well tolerated by all patients.
Conclusions: Patients showing tumour progression while receiving [177Lu]Lu-PSMA-I&T radioligand therapy may benefit from rescue therapy with the novel radiohybrid PSMA ligand, [177Lu]Lu-rhPSMA-10.1. Higher tumour absorbed radiation doses with [177Lu]Lu-rhPSMA-10.1 may overcome primary and acquired radiation resistance.
期刊介绍：
The European Journal of Nuclear Medicine and Molecular Imaging serves as a platform for the exchange of clinical and scientific information within nuclear medicine and related professions. It welcomes international submissions from professionals involved in the functional, metabolic, and molecular investigation of diseases. The journal's coverage spans physics, dosimetry, radiation biology, radiochemistry, and pharmacy, providing high-quality peer review by experts in the field. Known for highly cited and downloaded articles, it ensures global visibility for research work and is part of the EJNMMI journal family.
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