This grant combines an integrated set of laboratory science and clinical investigations specifically focused on improving the ability to diagnostically image and potentially treat human cancer using radiolabeled monoclonal antibodies. In Aim 1 we will develop improved methods of antibody radioiodination using an iodinated tyramine-cellobiose (TCB) adduct, designed to produce increased retention of radioiodine in tumors. Labeling methods will be optimized for yields and preservation of immunoreactivity and products will be tested in tumor cell suspensions and in tumored mice. In Aim 2 we will attempt immunospecific lymphoscintigraphy of tumored nodes in patients with metastatic melanoma. We have demonstrated non-specific uptake of antibody in tumored nodes; this will be blocked with subcutaneous doses of cold irrelevant antibody prior to simultaneous injection of I-131 specific and I-125 non- specific antibody. After I-131 imaging excised nodes will be analyzed by counting and dual isotope autoradiography. In Aim 3 we will extend our work on antibody imaging of documented melanoma and eventually cancers of the lung and breast. Using diagnostic doses of I-131 labeled antibody we will carefully measure biodistribution and tumor labeling and make estimates of internal radiation absorbed doses. We will determine if the quality of imaging and tumor deposition of antibody radiolabeled by the para- iodophenyl and tyramine-cellobiose methods is improved compared to chloramine-T labeled antibody. In Aim 4 we will select patients who show good tumor uptake with I-131 antibody and treat them with single high doses of I-131 antibody. To circumvent bone marrow damage with this treatment, patients will have marrow stored prior to therapy and reinfused afterward.
NIH ExPorter
NIH ExPorter