The synthesis and evaluation of bifunctional chelating agents designed to sequester gallium(III) isotopes define the general scope of the project. Taking advantage of the extensive chemical literature elucidating the coordinating chemistry of Ga(III), we targeted two compounds as promising candidates for attaching Ga(III) isotopes to monoclonal antibody. The first, a ligand incorporating three catechol binding subunits, forms a trianionic complex with trivalent ions and is expected to display considerable stability at physiological pH. 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 p-NCS-Bz-NOTA has recently been 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 assess the in vitro and in vivo stability of the Ga(III) complexes and the immunoconjugates. Preliminary experiments show that both compounds are efficiently labeled with In-111, and serum stability studies are underway.
