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: one is a tumor virus induced leukemia of mice; another is human tumor xenographs in nude athymic mice. 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 nuclidic properties available, thus Copper-67 represents a weak, short range, low energy beta emitter, Yttrium-90 is a long range, high energy beta emitter, Bismuth-212 is a short-lived, alpha emitter and Lead-212 provides both short and long range beta emissions and the subsequent alpha emission of its Bismuth-212 daughter. The syntheses of the chelating agents required for linkage of these isotopes to antibody is now complete. A new compound, (Bi-CHX-DTPA), was synthesized and shown to be useful for labeling monoclonal antibodies with Bi-212. A therapy study in leukemic mice has been accomplished. These studies will provide for human medicine a basis for design of rational therapy of malignancies by selectively targeting cytocidal agents to tumors, as well as metastases and as well will allow improved diagnostic imaging of malignancies.
