Harnessing <sup>64</sup> Cu/ <sup>67</sup> Cu for a theranostic approach to pretargeted radioimmunotherapy
Outi Keinänen, 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
Abstract
Significance Radioimmunotherapy is predicated on harnessing the exquisite specificity of antibodies to deliver cytotoxic radiation to tumors. Yet the long circulation time of radioimmunoconjugates leads to high radiation doses to healthy tissues. Pretargeted radioimmunotherapy (PRIT) circumvents this problem by decoupling the antibody and radionuclide, injecting the former prior to the latter, and empowering the two components to combine at the tumor. We have leveraged bioorthogonal click chemistry, a colorectal cancer-targeting antibody, and a pair radioligands bearing radioisotopes of copper—positron-emitting copper-64 and beta particle-emitting copper-67—to create a pretargeting system that enables both theranostic positron emission tomography and PRIT. We believe that the incorporation of theranostic imaging into PRIT regimens could be instrumental in the clinical success of the modality.