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Compared with tumor tissue biopsy, it supports serial profiling of genetic and molecular changes across treatment time points, enabling assessment of recurrence, drug resistance, and response. Radiopharmaceutical therapy targeting PSMA has expanded since 2022, and emerging evidence supports liquid biopsy as a promising adjunct for evaluating PSMA radiopharmaceutical therapy by identifying PSMA-negative CTCs and ctDNA alterations linked to resistance and survival outcomes.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/liquid-biopsy-of-circulating-tumor-cells-and-dna-in-the-context-of-psma-radiopharmaceutical-therapy/439293/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/liquid-biopsy-of-circulating-tumor-cells-and-dna-in-the-context-of-psma-radiopharmaceutical-therapy/439293.png","ImageObject",300,407,{"name":92,"@type":93},"Aria Callaghan","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-02","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What does liquid biopsy analyze in cancer patients?","Question",{"text":112,"@type":113},"Liquid biopsy analyzes circulating tumor cells (CTCs) and smaller cancer-derived components such as circulating tumor DNA (ctDNA) and cell-free DNA released into body fluids.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why is liquid biopsy considered valuable compared with solid-tumor biopsy?",{"text":117,"@type":113},"It allows serial sampling over time, providing opportunities to profile genetic and molecular tumor changes during treatment or monitoring at different time points.",{"name":119,"@type":110,"acceptedAnswer":120},"How can ctDNA findings relate to resistance or outcomes in PSMA radiopharmaceutical therapy?",{"text":121,"@type":113},"The text reports that specific ctDNA alterations can be associated with resistance and reduced benefit, including gene amplifications (e.g., FGFR1, CCNE1) and alterations in androgen receptor or PI3K pathway genes, as well as survival associations with aggressive variant prostate cancer gene changes.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},439293,1790950532,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":81,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":39},962084926284,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Liquid Biopsy of Circulating Tumor Cells and DNA in the Context of PSMA Radiopharmaceutical Therapy  \nAdrien Holzgreve1,2, Christine E. Mona 1,3, Koichiro Kimura 1, Xinmin Li3,4, Yazhen Zhu3–5, Hsian-Rong Tseng3,5, John K. Lee3,6,7, Alexandra Drakaki3,6, Isla P. Garraway3,8,9, Matthew B. Rettig3,8,10, Jeremie Calais* 1,3, and Ali Salavati*1,3  \n1Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California; 2Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; 3Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California; 4Department of Pathology and Laboratory Medicine, UCLA Technology Center for Genomics and Bioinformatics, Los Angeles, California; 5California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California; 6Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California; 7Molecular Biology Institute, UCLA, Los Angeles, California; 8Department of Urology, David Geffen School of Medicine, UCLA, Los Angeles, California; 9Department of Surgical and Perioperative Care, VA Greater Los Angeles Healthcare System, Los Angeles, California; and 10Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, California  \noegyconandcepistboeig“qutudidiedbposrye” haas itggainradedualhilyghgetinteresting inoporated in patient care for multiple cancer types. Liquid biopsy describes the analysis of circulating tumor cells (CTCs) or smaller pieces of cancer cells such as circulating tumor DNA (ctDNA) and cell-free DNA that have been released into body fluids, for example into circulation. Although tumor biopsy is the gold standard in cancer diagnosis, liquid biopsy allows for serial sampling that gives the opportunity for profiling of genetic and molecular changes taking place in a tumor at different time points during treatment or monitoring of the disease. Other potential applications include but are not limited to initial indication of cancer diagnosis, disease recurrence, assessment of drug resistance, and monitoring of treatment response. Although only 7 oncology liquid biopsy trials were reported to have been initiated in 2007, the number had grown to approximately 200 trials by 2022, correlating with the increased number of targeted drugs in development and the lower cost of sequencing (1) .  \nRadiopharmaceutical therapy (RPT) targeting prostate-specific membrane antigen (PSMA) has been increasingly used in clinical practice and trials since its approval for patients with metastatic castration-resistant prostate cancer (mCRPC) in 2022 . Liquid biopsy is evolving as a promising addition in the evaluation of PSMA RPT, as preliminary data have provided the rationale for further investigation.  \nReceived Jun. 17, 2025; revision accepted Oct. 15, 2025 .  \nFor correspondence, contact Adrien Holzgreve (aholzgreve@mednet.ucla. edu) .  \n*Contributed equally to this work.  \nPublished online Nov. 13, 2025 .  \nImmediate Open Access: Creative Commons Attribution 4.0 International License (CC BY) allows users to share and adapt with attribution, excluding materials credited to previous publications. License: [https://creativecommons](https://creativecommons). org/licenses/by/4.0/. Details: [https://jnm.snmjournals.org/page/permissions](https://jnm.snmjournals.org/page/permissions).  \nCOPYRIGHT 􀀁 2026 by the Society of Nuclear Medicine and Molecular Imaging. DOI: 10.2967/jnumed.125.270651  \nIn a prospective proof-of-principle study of 20 patients treated with [177Lu]Lu-PSMA-617, 20% of CTC samples showed no PSMA expression, despite unequivocal PSMA expression of solid metastases in PET (2) . A high fraction of PSMA-negative CTCs was linked to both shorter overall and shorter progression-free survival (2) . Pretreatment ctDNA findings in a cohort of 44","cbCaimKZsDk81f8P","https://ap.wps.com/l/cbCaimKZsDk81f8P","pdf",669854,"English","# Background and rationale\n## Liquid biopsy concept and clinical applications\n## PSMA radiopharmaceutical therapy and emerging role of liquid biopsy\n# Evidence and biomarker findings\n## CTC PSMA expression and survival impact\n## ctDNA gene amplification and resistance to PSMA therapy\n## Genetic alterations and treatment benefit\n## ctDNA fraction, trial subanalyses, and predictive value","[{\"question\":\"What does liquid biopsy analyze in cancer patients?\",\"answer\":\"Liquid biopsy analyzes circulating tumor cells (CTCs) and smaller cancer-derived components such as circulating tumor DNA (ctDNA) and cell-free DNA released into body fluids.\"},{\"question\":\"Why is liquid biopsy considered valuable compared with solid-tumor biopsy?\",\"answer\":\"It allows serial sampling over time, providing opportunities to profile genetic and molecular tumor changes during treatment or monitoring at different time points.\"},{\"question\":\"How can ctDNA findings relate to resistance or outcomes in PSMA radiopharmaceutical therapy?\",\"answer\":\"The text reports that specific ctDNA alterations can be associated with resistance and reduced benefit, including gene amplifications (e.g., FGFR1, CCNE1) and alterations in androgen receptor or PI3K pathway genes, as well as survival associations with aggressive variant prostate cancer gene changes.\"}]","Liquid Biopsy of Circulating Tumor Cells and DNA in the Context of PSMA Radiopharmaceutical Therapy | PDF",1790688077]