Harnessing (64)Cu/(67)Cu for a theranostic approach to pretargeted radioimmunotherapy Journal Article
| Authors: | Keinänen, 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. |
| Article Title: | Harnessing (64)Cu/(67)Cu for a theranostic approach to pretargeted radioimmunotherapy |
| Abstract: | Over 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. Copyright © 2020 the Author(s). Published by PNAS. |
| Keywords: | positron emission tomography; radioimmunotherapy; theranostics; pretargeted radioimmunotherapy; pretargeting |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 117 |
| Issue: | 45 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2020-11-10 |
| Start Page: | 28316 |
| End Page: | 28327 |
| Language: | English |
| DOI: | 10.1073/pnas.2009960117 |
| PUBMED: | 33106429 |
| PROVIDER: | scopus |
| PMCID: | PMC7668034 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2020 -- Source: Scopus |
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