{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T21:51:14Z","timestamp":1781301074129,"version":"3.54.1"},"reference-count":53,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"New Frontiers in Research Fund\u2014Transformation","award":["NFRFT-2022-00269"],"award-info":[{"award-number":["NFRFT-2022-00269"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prostate cancer (PCa), particularly in its metastatic form, remains a major clinical challenge due to limited diagnostic and therapeutic options. To address this, we developed a novel radiotheranostic agent, [64Cu]Cu-NOTA-TP-PSMA, by conjugating a prostate-specific membrane antigen (PSMA) ligand to a 64Cu-radiolabeled terpyridine-platinum (TP) compound previously shown to exert selective cytotoxicity against cancer cells. In this study, the biological performance of [64Cu]Cu-NOTA-TP-PSMA was compared with the monomeric analogs [64Cu]Cu-NOTA-PSMA and [64Cu]Cu-NOTA-TP through in vitro studies in PSMA-positive LNCaP prostate cancer cells and non-malignant HEK-293 cells. [64Cu]Cu-NOTA-TP-PSMA showed high stability, PSMA binding affinity and exhibited substantially enhanced uptake, internalization, retention, and nuclear localization in LNCaP cells relative to the monomers, whereas uptake and nuclear accumulation in HEK-293 cells were negligible. Cytotoxicity assays further demonstrated potent and selective activity in LNCaP cells, with EC50 values in the low nanomolar range, and minimal toxicity in HEK-293 cells. Collectively, these results identify [64Cu]Cu-NOTA-TP-PSMA as a promising radiotheranostic agent, warranting further in vivo evaluation for prostate cancer imaging and targeted radiotherapy.<\/jats:p>","DOI":"10.3390\/ijms262311651","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T08:49:22Z","timestamp":1764665362000},"page":"11651","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development and In Vitro Evaluation of [64Cu]Cu-NOTA-TP-PSMA, a Novel Radiotheranostic Agent Against Prostate Cancer"],"prefix":"10.3390","volume":"26","author":[{"given":"Hoda","family":"Talebian","sequence":"first","affiliation":[{"name":"Department of Medical Imaging and Radiation Sciences, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia","family":"Ait-Mohand","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiation Sciences, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prenitha Mercy","family":"Ignatius Arokia Doss","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiation Sciences, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0938-439X","authenticated-orcid":false,"given":"L\u00e9on","family":"Sanche","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiation Sciences, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"},{"name":"Institut de Recherche sur le Cancer de l\u2019Universit\u00e9 de Sherbrooke (IRCUS), Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0319-4512","authenticated-orcid":false,"given":"Brigitte","family":"Gu\u00e9rin","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiation Sciences, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"},{"name":"Institut de Recherche sur le Cancer de l\u2019Universit\u00e9 de Sherbrooke (IRCUS), Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"},{"name":"Sherbrooke Molecular Imaging Center (CIMS), Centre de Recherche du CHUS (CRCHUS), Sherbrooke, QC J1H 5H3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s40164-023-00444-9","article-title":"Recent Advances and Future Perspectives in the Therapeutics of Prostate Cancer","volume":"12","author":"Varaprasad","year":"2023","journal-title":"Exp. 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