The purpose of the proposed study is to continue our evaluation of the therapy of malignant disease with radiolabeled antibodies. We will use I131-labeled anti-Thy 1.1 monoclonal antibodies to treat established AKR/J Thy 1.1+ lymphomas growing in AKR/Cu (Thy 1.2+) mice, where the target antigen is tumor specific, and in AKR/J (Thy 1.1+) mice, where the target antigen is expressed on normal T-cells in addition to tumor. Preliminary studies have shown that such treatment is effective against subcutaneous tumor in a setting where antibody is tumor specific. We now propose to examine the factors influencing the delivery of radiation to a solid tumor including the immunologic and pharmacologic characteristics of the carrier antibody molecule, as well as the distribution of the target antigen on both normal and malignant cells. The efficacy and toxicity of I131-antibody regimens delivering radiation to tumor at varying dose rates will be studied. The results of these studies should help elucidate principals governing therapy with radiolabeled antibodies and facilitate design of future clinical trials in humans.
