{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:45:29Z","timestamp":1791909929033,"version":"4.3.4"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"French \u201cLigue contre le Cancer, Comit\u00e9 du Puy de D\u00f4me\u201d"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The development of 64Cu-based immuno-PET radiotracers requires the use of copper-specific bifunctional chelators (BFCs) that contain functional groups allowing both convenient bioconjugation and stable copper complexes to limit in vivo bioreduction, transmetallation and\/or transchelation. The excellent in vivo kinetic inertness of the pentaazamacrocyclic [64Cu]Cu-15-5 complex prompted us to investigate its potential for the 64Cu-labelling of monoclonal antibodies (mAbs), compared with the well-known NODAGA and DOTA chelators. To this end, three NODAGA, DOTA and 15-5-derived BFCs, containing a pendant azadibenzocyclooctyne moiety, were synthesised and a robust methodology was determined to form covalent bonds between them and azide-functionalised trastuzumab, an anti-HER2 mAb, using strain-promoted azide-alkyne cycloaddition. Unlike the DOTA derivative, the NODAGA- and 15-5-mAb conjugates were radiolabelled with 64Cu, obtaining excellent radiochemical yields, under mild conditions. Although all the radioimmunoconjugates showed excellent stability in PBS or mouse serum, [64Cu]Cu-15-5- and [64Cu]Cu-NODAGA-trastuzumab presented higher resistance to transchelation when challenged by EDTA. Finally, the immunoreactive fraction of the radioimmunoconjugates (88\u201394%) was determined in HER-2 positive BT474 human breast cancer cells, confirming that the bioconjugation and radiolabelling processes implemented had no significant impact on antigen recognition.<\/jats:p>","DOI":"10.3390\/molecules28010075","type":"journal-article","created":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T03:26:25Z","timestamp":1671765985000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Synthesis and In Vitro Comparison of DOTA, NODAGA and 15-5 Macrocycles as Chelators for the 64Cu-Labelling of Immunoconjugates"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0520-9156","authenticated-orcid":false,"given":"Aur\u00e9lie","family":"Maisonial-Besset","sequence":"first","affiliation":[{"name":"Universit\u00e9 Clermont Auvergne, Inserm, Imagerie Mol\u00e9culaire et Strat\u00e9gies Th\u00e9ranostiques, UMR 1240, F-63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Witkowski","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Clermont Auvergne, Inserm, Imagerie Mol\u00e9culaire et Strat\u00e9gies Th\u00e9ranostiques, UMR 1240, F-63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Quintana","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Clermont Auvergne, Inserm, Imagerie Mol\u00e9culaire et Strat\u00e9gies Th\u00e9ranostiques, UMR 1240, F-63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Besse","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Clermont Auvergne, Inserm, Imagerie Mol\u00e9culaire et Strat\u00e9gies Th\u00e9ranostiques, UMR 1240, F-63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8880-5764","authenticated-orcid":false,"given":"Vincent","family":"Gaumet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Clermont Auvergne, Inserm, Imagerie Mol\u00e9culaire et Strat\u00e9gies Th\u00e9ranostiques, UMR 1240, F-63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Cordonnier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Clermont Auvergne, Inserm, Imagerie Mol\u00e9culaire et Strat\u00e9gies Th\u00e9ranostiques, UMR 1240, F-63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrille","family":"Alliot","sequence":"additional","affiliation":[{"name":"GIP Arronax, F-44800 Saint-Herblain, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"Vidal","sequence":"additional","affiliation":[{"name":"GIP Arronax, F-44800 Saint-Herblain, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9901-7608","authenticated-orcid":false,"given":"Caroline","family":"Denevault-Sabourin","sequence":"additional","affiliation":[{"name":"GICC EA7501, Team IMT, Universit\u00e9 de Tours, UFR de M\u00e9decine, B\u00e2timent Vialle, 10 Boulevard Tonnell\u00e9, BP 3223, CEDEX 01, 37032 Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Tarrit","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Clermont Auvergne, Inserm, Imagerie Mol\u00e9culaire et Strat\u00e9gies Th\u00e9ranostiques, UMR 1240, F-63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Levesque","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Jean Perrin Comprehensive Cancer Centre, F-63011 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Miot-Noirault","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Clermont Auvergne, Inserm, Imagerie Mol\u00e9culaire et Strat\u00e9gies Th\u00e9ranostiques, UMR 1240, F-63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7162-8450","authenticated-orcid":false,"given":"Jean-Michel","family":"Chezal","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Clermont Auvergne, Inserm, Imagerie Mol\u00e9culaire et Strat\u00e9gies Th\u00e9ranostiques, UMR 1240, F-63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.molimm.2015.04.001","article-title":"In vivo imaging with antibodies and engineered fragments","volume":"67","author":"Freise","year":"2015","journal-title":"Mol. 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