Efficient Bifunctional Decadentate Ligand 3p-C-DEPA for Targeted α-Radioimmunotherapy Applications

A new bifunctional ligand 3p-C-DEPA was synthesized and evaluated for use in targeted alpha-radioimmunotherapy. 3p-C-DEPA was efficiently prepared via regiospecific ring opening of an aziridinium ion and conjugated with trastuzumab. The 3p-C-DEPA-trastuzumab conjugate was extremely rapid in binding Bi-205/6, and the corresponding Bi-205/6-3p-C-DEPA-trastuzumab complex was stable in human serum. Biodistribution studies were performed to evaluate in vivo stability and tumor targeting of Bi-205/6-3p-C-DEPA-trastuzumab conjugate in tumor bearing athymic mice. Bi-205/6-3p-C-DEPA-trastuzumab conjugate displayed excellent in vivo stability and targeting as evidenced by low organ uptake and high tumor uptake. The results of the in vitro and in vivo studies indicate that 3p-C-DEPA is a promising chelator for radioimmunotherapy of Bi-212 and Bi-213.