Synthesis and evaluation of a macrocyclic bifunctional chelating agent for use with bismuth radionuclides

The detailed synthesis of the bifunctional chelating agent 2-( p-isothiocyanatobenzyl)-1,4,7,10,13-pentaazacyclopentadecane-N,N′,N″,N‴,N″″-pentaacetic acid (BF_PEPA) is reported. This ligand was conjugated to monoclonal antibody B3 and the resultant immunoconjugate radiolabeled with 205,206Bi. The in vivo stability of the radiolabeled immunoconjugate, and targeting characteristics were determined by biodistribution studies in A431 xenograft tumor-bearing mice sacrificed at 0.5, 1, 2, 4, and 24 hr. Results indicate that BF_PEPA appears to not be a suitable bifunctional chelating agent for sequestering isotopes of Bi(III) for radioimmunotherapy applications.