The use of monoclonal antibodies for radioimmunoimaging and immunotherapy will be investigated in two animal tumor systems: a tumor virus-induced leukemia of mice and human colonic carcinoma xenografts in hamsters. Radioimmunoimaging of tumors with antibodies labeled with I311 will be compared to radiometal (In111, Sc47, Ga67, and Tc99m) chelate-conjugated antibodies. Several derivatives including the carboxycarbonic anhydride and the bicyclic anhydride of DTPA and the isothiocyanate of EDTA have been prepared and will be evaluated for yield of incorporation and stability of isotope. Methods for chelating the radiometal prior to conjugation with antibody will be developed to eliminate adventitious binding of isotope to immunogloblin. The kinetics of tumor targeting, quality of image, catabolism, and toxicities will be evaluated. Alpha- and beta-emitting isotypes and toxins will be coupled to immunoglobulins for use in specific targeting of cytocidal agents to tumors. The therapeutic efficacy of antibodies labeled with the beta-emitting I131 and Sc47 will be compared to the alpha-emitting Bi212. Sequential therapy will also be evaluated. Isotopic therapy will be compared to immunotoxin therapy with respect to reduction of tumor burden, prolonging survival, eradication of metastases, and toxicity. These studies will provide a rational basis for imaging and therapy of malignancies relevant to clinical practice.
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