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 ligands were targeted as promising candidates for attaching Ga(III) isotopes to monoclonal antibodies. The first 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. Synthesis of a C-functionalized para-SCN-Bz-NOTA and an N-functionalized para-SCN-phenpropyl-NOTA were recently completed, both compounds in a C-14 labeled and in a high purity C-12 form suitable for clinical experiments. With both target compounds now in hand, the in vitro and in vivo stability of the Ga(III) and In(III) complexes of both ligands and their respective immunoconjugates were assessed. Preliminary experiments indicate that both compounds are efficiently labeled with In-111 and Ga-67. Biodistribution experiment and serum stability studies have indicated that the C-functionalized NOTA Ga-67 complex may be somewhat more stable in vivo versus the N-functionalized NOTA while neither compound appears as useful as the disusbstituted DTPA (1B4M-DTPA) for binding In-111 in vivo.
