actinium Ac 225 FPI-2068

A radioimmunoconjugate composed of FPI-2053, a humanized bispecific antibody targeting epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (HGFR; c-Met), chelated to the bifunctional, macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA), and radiolabeled with the alpha-emitting radionuclide actinium Ac 225, with potential antineoplastic activity. Upon administration of actinium Ac 225 FPI-2068, the FPI-2053 moiety targets and binds to the extracellular domains of both EGFR and c-Met expressed on certain cancer cells, thereby delivering a cytotoxic dose of alpha radiation directly into EGFR- and c-Met-expressing tumor cells. Additionally, the induction of apoptosis and subsequent release of tumor-associated antigens (TAAs) from the tumor cells may induce an anti-tumor immune response, thereby further killing tumor cells. EGFR and c-Met, both upregulated or mutated in a variety of tumor cell types, play key roles in tumor cell proliferation. EGFR and c-Met are co-expressed on the surface of various cancer cell types while co-expression on normal, healthy cells is minimal.