{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:36:52Z","timestamp":1790779012194,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Institute of Health Research","award":["PJT-162325"],"award-info":[{"award-number":["PJT-162325"]}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2019-05284"],"award-info":[{"award-number":["RGPIN-2019-05284"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Maximum benefits of chemoradiation therapy with platinum-based compounds are expected if the radiation and the drug are localized simultaneously in cancer cells. To optimize this concomitant effect, we developed the novel chemoradiotherapeutic agent [64Cu]Cu-NOTA-C3-TP by conjugating, via a short flexible alkyl chain spacer (C3), a terpyridine platinum (TP) moiety to a NOTA chelator complexed with copper-64 (64Cu). The decay of 64Cu produces numerous low-energy electrons, enabling the 64Cu-conjugate to deliver radiation energy close to TP, which intercalates into G-quadruplex DNA. Accordingly, the in vitro internalization kinetic and the cytotoxic activity of [64Cu]Cu-NOTA-C3-TP and its derivatives were investigated with colorectal cancer (HCT116) and normal human fibroblast (GM05757) cells. Radiolabeling by 64Cu results in a &gt;55,000-fold increase of cytotoxic potential relative to [NatCu]Cu-NOTA-C3-TP at 72 h post administration, indicating a large additive effect between 64Cu and the TP drug. The internalization and nucleus accumulation of [64Cu]Cu-NOTA-C3-TP in the HCT116 cells were, respectively, 3.1 and 6.0 times higher than that for GM05757 normal human fibroblasts, which is supportive of the higher efficiency of the [64Cu]Cu-NOTA-C3-TP for HCT116 cancer cells. This work presents the first proof-of-concept study showing the potential use of the [64Cu]Cu-NOTA-C3-TP conjugate as a targeted chemoradiotherapeutic agent to treat colorectal cancer.<\/jats:p>","DOI":"10.3390\/nano11092154","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T04:43:43Z","timestamp":1629780223000},"page":"2154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Design, Synthesis, and Cytotoxicity Assessment of [64Cu]Cu-NOTA-Terpyridine Platinum Conjugate: A Novel Chemoradiotherapeutic Agent with Flexible Linker"],"prefix":"10.3390","volume":"11","author":[{"given":"Meysam","family":"Khosravifarsani","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine and Radiobiology, 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 Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2117-8372","authenticated-orcid":false,"given":"Benoit","family":"Paquette","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Radiobiology, 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 Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0319-4512","authenticated-orcid":false,"given":"Brigitte","family":"Gu\u00e9rin","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"},{"name":"Sherbrooke Molecular Imaging Center (CIMS), CRCHUS, 3001, 12e Avenue Nord, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ejphar.2014.07.025","article-title":"Cisplatin in cancer therapy: Molecular mechanisms of action","volume":"740","author":"Dasari","year":"2014","journal-title":"Eur. 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