Kilian Kluge, David Haberl, Alexander Haug, Lukas Kenner, Gero Kramer, Shahrokh Shariat, Katarina Kumpf, Marcus Hacker
{"title":"基因组不稳定性与[¹⁷⁷Lu]Lu-PSMA-I&T放射性配体疗法的反应有关：一项探索性的初步液体活检分析","authors":"Kilian Kluge, David Haberl, Alexander Haug, Lukas Kenner, Gero Kramer, Shahrokh Shariat, Katarina Kumpf, Marcus Hacker","doi":"10.1007/s00259-025-07280-5","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>PSMA-targeted radioligand therapies (PSMA RLT) are an effective and safe option for metastatic castration-resistant prostate cancer, but responsive subtypes and their biomarkers are not fully defined.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Plasma samples for cell-free DNA (cfDNA) analysis were collected from 17 patients undergoing [¹⁷⁷Lu]Lu-PSMA-I&T. CfDNA underwent whole-genome sequencing to establish copy number variation (CNV) profiles and circulating-tumor DNA (ctDNA) levels and compared between prostate-specific antigen (PSA) response- and 1-year overall survival (1YOS) groups.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Non-responders exhibited higher degrees of cfDNA CNV burden (<i>P</i> = 0.048) and higher ctDNA levels (<i>P =</i> 0.036) than responders. Both markers allowed for the differentiation of responses (AUC: 0.792, 0.806) and 1YOS (AUC: 0.778, 0.847).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Unresponsive patients exhibited higher levels of cfDNA genomic instability and ctDNA levels, warranting genome-wide CNV profiling studies next to targeted approaches for mechanistic radiobiological insights and their value as response biomarkers for PSMA RLTs.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"17 1","pages":""},"PeriodicalIF":8.6000,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genomic instability is associated with response to [¹⁷⁷Lu]Lu-PSMA-I&T radioligand therapy: an exploratory, preliminary liquid biopsy analysis\",\"authors\":\"Kilian Kluge, David Haberl, Alexander Haug, Lukas Kenner, Gero Kramer, Shahrokh Shariat, Katarina Kumpf, Marcus Hacker\",\"doi\":\"10.1007/s00259-025-07280-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Background</h3><p>PSMA-targeted radioligand therapies (PSMA RLT) are an effective and safe option for metastatic castration-resistant prostate cancer, but responsive subtypes and their biomarkers are not fully defined.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>Plasma samples for cell-free DNA (cfDNA) analysis were collected from 17 patients undergoing [¹⁷⁷Lu]Lu-PSMA-I&T. CfDNA underwent whole-genome sequencing to establish copy number variation (CNV) profiles and circulating-tumor DNA (ctDNA) levels and compared between prostate-specific antigen (PSA) response- and 1-year overall survival (1YOS) groups.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>Non-responders exhibited higher degrees of cfDNA CNV burden (<i>P</i> = 0.048) and higher ctDNA levels (<i>P =</i> 0.036) than responders. Both markers allowed for the differentiation of responses (AUC: 0.792, 0.806) and 1YOS (AUC: 0.778, 0.847).</p><h3 data-test=\\\"abstract-sub-heading\\\">Conclusion</h3><p>Unresponsive patients exhibited higher levels of cfDNA genomic instability and ctDNA levels, warranting genome-wide CNV profiling studies next to targeted approaches for mechanistic radiobiological insights and their value as response biomarkers for PSMA RLTs.</p><h3 data-test=\\\"abstract-sub-heading\\\">Graphical Abstract</h3>\",\"PeriodicalId\":11909,\"journal\":{\"name\":\"European Journal of Nuclear Medicine and Molecular Imaging\",\"volume\":\"17 1\",\"pages\":\"\"},\"PeriodicalIF\":8.6000,\"publicationDate\":\"2025-04-22\",\"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/s00259-025-07280-5\",\"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/s00259-025-07280-5","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}
Genomic instability is associated with response to [¹⁷⁷Lu]Lu-PSMA-I&T radioligand therapy: an exploratory, preliminary liquid biopsy analysis
Background
PSMA-targeted radioligand therapies (PSMA RLT) are an effective and safe option for metastatic castration-resistant prostate cancer, but responsive subtypes and their biomarkers are not fully defined.
Methods
Plasma samples for cell-free DNA (cfDNA) analysis were collected from 17 patients undergoing [¹⁷⁷Lu]Lu-PSMA-I&T. CfDNA underwent whole-genome sequencing to establish copy number variation (CNV) profiles and circulating-tumor DNA (ctDNA) levels and compared between prostate-specific antigen (PSA) response- and 1-year overall survival (1YOS) groups.
Results
Non-responders exhibited higher degrees of cfDNA CNV burden (P = 0.048) and higher ctDNA levels (P = 0.036) than responders. Both markers allowed for the differentiation of responses (AUC: 0.792, 0.806) and 1YOS (AUC: 0.778, 0.847).
Conclusion
Unresponsive patients exhibited higher levels of cfDNA genomic instability and ctDNA levels, warranting genome-wide CNV profiling studies next to targeted approaches for mechanistic radiobiological insights and their value as response biomarkers for PSMA RLTs.
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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