Our extensive experience with radiolabeled antibody therapy has led to encouraging results in studies of the therapy of lymphoma and leukemia. The quantitative imaging data obtained in these studies have also identified several issues critical for improving the relative amount of radiation delivered to tumor compared to normal tissues in order to augment the therapeutic effect. We propose to address these issues by first assessing the relative biodistribution of antibodies that are internalized or not internalized using human tumor xenografts in SCID mice as well as normal organs as targets, and testing the advantage of conjugating antibodies with alternative radiolabels that will lead to intracellular retention of radioactivity (Aims 1 and 2). We will also develop quantitative imaging methods for alternative therapeutic radioisotopes to provide accurate assessment of radiolabeled antibody biodistribution in patients (Aim 3). Based on results of these preclinical experiments, we will select alternative radionuclide antibody combinations for comparison with those currently used in Projects I and II (Aim 4).
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