Resumen
Monoclonal antibodies (IgG) are excellent probes for targeting cell surface receptors for imaging and therapeutic applications. These theranostic agents are often developed by randomly conjugating radioisotopes/drugs/chelators to the primary amine of lysine or the sulfhydryl groups of cysteine on the antibody. Random conjugation often alters the properties of the antibody. We have site-specifically radiolabeled nimotuzumab an anti-epidermal growth factor receptor (EGFR) monoclonal antibody with 89Zr and 225Ac using SpyTag: ?N-SpyCatcher for positron emission tomography (PET) imaging and alpha particle radiotherapy, and evaluated these agents in a model of EGFR-positive triple negative breast cancer (TNBC). Nimotuzumab-SpyTag-?N-SpyCatcher constructs showed improved binding in vitro compared with randomly conjugated constructs. 89Zr-nimotuzumab-SpyTag-?N-SpyCatcher specifically delineated EGFR-positive xenograft in vivo using microPET/CT imaging. Compared with control treatment groups, 225Ac-nimotuzumab-SpyTag-?N-SpyCatcher more than doubled the survival of mice bearing EGFR-positive MDA-MB-231 TNBC xenograft. This work highlights a facile method to site-specifically radiolabel antibodies using SpyTag: ?N-SpyCatcher.