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. Thus, Copper-67 is a weak, short range beta emitter. Yttrium-90 is a long range, high energy beta emitter and Bismuth-212 is a short range alpha emitter. The compound cyclohexyl DTPA was recently tested and used for radioimmunotherapy of the Rauscher leukemia in mice. Efficacy was exceptional in that complete remission of disease was induced with no histological evidence of toxicity. We are currently engineering a scaled-up process to deliver larger doses of Bismuth-212 for future clinical trials which will involve installation and use of a hot cell. We anticipate that this facility will be on-line within the next fiscal year. 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.
