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dc.contributor.authorKeinanen, O
dc.contributor.authorFung, K
dc.contributor.authorBrennan, JM
dc.contributor.authorZia, N
dc.contributor.authorHarris, M
dc.contributor.authorvan Dam, E
dc.contributor.authorBiggin, C
dc.contributor.authorHedt, A
dc.contributor.authorStoner, J
dc.contributor.authorDonnelly, PS
dc.contributor.authorLewis, JS
dc.contributor.authorZeglis, BM
dc.date.accessioned2020-11-26T23:29:33Z
dc.date.available2020-11-26T23:29:33Z
dc.date.issued2020-11-10
dc.identifierpii: 2009960117
dc.identifier.citationKeinanen, O., Fung, K., Brennan, J. M., Zia, N., Harris, M., van Dam, E., Biggin, C., Hedt, A., Stoner, J., Donnelly, P. S., Lewis, J. S. & Zeglis, B. M. (2020). Harnessing Cu-64/Cu-67 for a theranostic approach to pretargeted radioimmunotherapy. Proceedings of the National Academy of Sciences of the United States of America, 117 (45), pp.28316-28327. https://doi.org/10.1073/pnas.2009960117.
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/11343/252244
dc.description.abstractOver the past decade, theranostic imaging has emerged as a powerful clinical tool in oncology for identifying patients likely to respond to targeted therapies and for monitoring the response of patients to treatment. Herein, we report a theranostic approach to pretargeted radioimmunotherapy (PRIT) based on a pair of radioisotopes of copper: positron-emitting copper-64 (64Cu, t1/2 = 12.7 h) and beta particle-emitting copper-67 (67Cu, t1/2 = 61.8 h). This strategy is predicated on the in vivo ligation between a trans-cyclooctene (TCO)-bearing antibody and a tetrazine (Tz)-based radioligand via the rapid and bioorthogonal inverse electron-demand Diels–Alder reaction. Longitudinal therapy studies were conducted in a murine model of human colorectal carcinoma using an immunoconjugate of the huA33 antibody modified with TCO (huA33-TCO) and a 67Cu-labeled Tz radioligand ([67Cu]Cu-MeCOSar-Tz). The injection of huA33-TCO followed 72 h later by the administration of 18.5, 37.0, or 55.5 MBq of [67Cu]Cu-MeCOSar-Tz produced a dose-dependent therapeutic response, with the median survival time increasing from 68 d for the lowest dose to >200 d for the highest. Furthermore, we observed that mice that received the highest dose of [67Cu]Cu-MeCOSar-Tz in a fractionated manner exhibited improved hematological values without sacrificing therapeutic efficacy. Dual radionuclide experiments in which a single administration of huA33-TCO was followed by separate injections of [64Cu]Cu-MeCOSar-Tz and [67Cu]Cu-MeCOSar-Tz revealed that the positron emission tomography images produced by the former accurately predicted the efficacy of the latter. In these experiments, a correlation was observed between the tumoral uptake of [64Cu]Cu-MeCOSar-Tz and the subsequent therapeutic response to [67Cu]Cu-MeCOSar-Tz.
dc.languageEnglish
dc.publisherNational Academy of Sciences
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.titleHarnessing Cu-64/Cu-67 for a theranostic approach to pretargeted radioimmunotherapy
dc.typeJournal Article
dc.identifier.doi10.1073/pnas.2009960117
melbourne.affiliation.departmentSchool of Chemistry
melbourne.source.titleProceedings of the National Academy of Sciences of USA
melbourne.source.volume117
melbourne.source.issue45
melbourne.source.pages28316-28327
dc.rights.licenseCC BY-NC-ND
melbourne.elementsid1470727
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668034
melbourne.contributor.authorDonnelly, Paul
dc.identifier.eissn1091-6490
melbourne.accessrightsOpen Access


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