Tumor associated monoclonal antibodies are potential therapeutic agents as selective carriers of cytotoxic agents to malignant cells. We are testing this hypothesis in several animal model systems. The cytocidal agents being employed are various radionuclides. Their relative efficacy when conjugated to monoclonal antibodies is being assayed and compared to that of monoclonal antibodies alone or conjugated to toxins. The several radionuclides chosen for study span the range of radionuclidic properties available. Recent research has focused on clinical use of Yttrium-90, and on completing preclinical studies with the alpha particle emitting nuclides Bismuth-212 and Bismuth-213. Most recently, we have installed a Hot Cell in the radiation laboratory in order tb make high level activity (>10 mCi) doses of antibodies labeled with the Bismuth-212 alpha particle emitter. Studies of toxicity of Bismuth-212-antibody doses is underway in monkeys. Currently, 4 mCi doses have shown almost no blood or other toxicity. Based on these data, an IND for treatment of leukemia patients will be constructed. Studies like these are providing for human medicine a basis for design of rational therapies of malignancies by selectively targeting cytocidal agents to tumors, as well as metastases and will in addition allow improved diagnostic imaging of malignancies.
