Harnessing Cu-64/Cu-67 for a theranostic approach to pretargeted radioimmunotherapy
Outi Keinanen, Kimberly Fung, James M Brennan, Nicholas Zia, Matt Harris, Ellen van Dam, Colin Biggin, Amos Hedt, Jon Stoner, Paul S Donnelly, Jason S Lewis, Brian M Zeglis
Proceedings of the National Academy of Sciences of USA | NATL ACAD SCIENCES | Published : 2020
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 studie..View full abstract
Awarded by NIH
We thank the NIH for their generous support of Grants R01CA240963 (B.M.Z., J.S.L.), U01CA221046 (B.M. Z., J.S.L.), R01CA204167 (B.M.Z.), and R35 CA232130 (J.S.L.). The Thompson Family Foundation (JSL) as well as the Memorial Sloan Kettering Cancer Center Small Animal Imaging Core Facility and Radiochemistry and Molecular Imaging Probe Core, which are supported by NIH Awards P30 CA08748 and S10 RR020892-01, are also acknowledged.