The synthesis and evaluation of bifunctional chelating agents designed to sequester Ga (III) isotopes define the general scope of the project. Taking advantage of extensive chemical literature elucidating the coordination chemistry of Ga(III), two compounds were targeted as promising candidates for attaching Ga(III) isotopes to monoclonal antibodies. The first ligand incorporates three catechol binding subunits, forms a trianionic complex with trivalent ions, and is expected to possess considerable stability under physiological conditions. The second ligand is the macrocyclic polyaminocarboxylate NOTA, which is known to form an exceptionally stable neutral complex with Ga(III). A comparison of the relative efficacy of the two very different ligands should assist the evolution of optimal chelating agents for gallium. The synthesis of a C-functionalized para-SCN-Bz-NOTA was recently completed in both C-14 labeled and in high purity C-12 form suitable for clinical experiments should the need arise. With both target compounds now in hand, we can begin to asses the in vitro and in vivo stability of the Ga(III) complexes and the imunoconjugates. Preliminary experts show that both compounds are efficiently labeled with In-111, and serum stability studies are underway.
