Synthesis and evaluation of a novel bifunctional ligand 3o-C-NETA for Yttrium-90 and Lutetium-177.

A bifunctional ligand is an essential component for targeted cancer therapy using cytotoxic radionuclides. We report the synthesis and evaluation of a novel bifunctional ligand, 3o-C-NETA, designed for labeling a bioactive small molecule or an antibody with β-particle emitting radionuclides Y and Lu. 3o-C-NETA is an octadentate chelating agent and contains both a macrocyclic backbone (1,4,7-triazacyclononane, TACN) and pendant donor groups. 3o-C-NETA was efficiently synthesized via the regiospecific ring opening of a functionalized aziridinium ion with tert-Butyl protected NODA (1,4,7-triazacyclononane-1,4-diacetic acid) and evaluated for radiolabeling kinetics and in vitro complex stability with Y and Lu. The new bifunctional ligand (3o-C-NETA) rapidly bound to Y or Lu, and the corresponding Y- or Lu-labeled 3o-C-NETA remained stable in human serum for two weeks.