| Abstract: | Despite the use of near maximal doses of external beam total-body irradiation, many patients who received transplants for relapsed hematologic cancers will fail because of tumor recurrence following therapy. With the use of radioisotope-labeled monoclonal antibodies, a more directed delivery of systemic radiotherapy may be achieved; tumor cell kill is increased without increased toxicity. On the basis of this hypothesis, we have begun dosimetry studies in normal dogs using an anti-immune response-associated antibody (7.2) labeled with 131I. Compared with an irrelevant isotype-matched antibody, the blood concentration of 131I-labeled 7.2 fell rapidly over the first 3 hours and then cleared more slowly. During this time, there was specific localization of 131I-7.2 in lymph nodes, spleen, and marrow. On the basis of the concentration curves generated over 48 hours, administration of enough 131I-7.2 to deliver 10 Grays to the blood would result in radiation doses of 9.8, 16.3, and 32.3 Grays to liver, marrow, and spleen, respectively. The liver uptake of labeled 7.2 appeared to be the result of its direct antigen-specific binding to hepatic Kupffer cells rather than to the clearance by the liver of either antigen-antibody complexes or antibody-coated cells. Gastric or intestinal radiation toxicity may be a problem due to gastric excretion of free I following binding of 131I-7.2 and subsequent deiodination. |
