We have initiated a project with the intent of developing bifunctional chelates to specifically sequester trivalent radionuclides such as Gallium (III). Bifunctional chelates provide a means for conjugating radionuclides to monoclonal antibody, resulting in a potentially site-specific radiopharmaceutical. To this end, we have chosen to synthesize new bifunctional chelates which incorporate functionalized catechol (1, 2-dihydroxbenzene) binding subunits. Chelates of this type form highly stable 3:1 complexes with trivalent metals at physiological pH, yet typically have little affinity for divalent metals, thus making the tris (catecholates) inherently more selective complexing agents than the more familiar polyaminocarboxylates (e.g., EDTA). We have recently completed the synthesis of a new macrocyclic tris (catecholate) chelate which incorporates a side arm for attachment to monoclonal antibody. Preliminary thin layer chromatography evidence indicates the chelate efficiently extracts Ga-67 from Ga-67 (citrate) at pH 6.6. We have successfully linked the new bifunctional catecholate to monoclonal antibodies and have labeled the ligand with gallium and indium. Evaluations of immunoreactivities and initiation of animal tissue distributions have begun.
