The objective of this proposal is to develop a sensitive diagnostic nuclear medicine imaging procedure, using radiolabeled monoclonal antibodies to melanoma associated antigens, to stage the presence and extent of melanoma metastases to regional lymph nodes. Two anti-melanoma monoclonal antibodies, 225.28S and 763.24T, both reactive with different epitopes of a high molecular weight antigen present on 89% of primary melanomas, but on few other tissues, will be labeled with I-131. These antibodies, along with I-125 labeled non-specific antibody and our standard lmphoscintigraphic agent, Tc99m human serum albumin, will be administered subcutaneously at the site of primary melanoma excision in patients whose primary melanoma is antigen-positive and who are scheduled for lymph node dissection. To assure a relatively high probability of nodal metastases, Stage I patients with tumors greater than 2.5 mm thickness and Stage II patients will be evaluated initially. These patients will be scanned after injection of the radiopharmaceuticals, using both Tc99m and I-131 energy windows. Delayed images will also be obtained. A nodal dissection will be carried out, directed by the results of our standard imaging agent and the clinical findings. Nodes resected will be carefully marked for location, and scan findings of both I-131 and Tc99m HSA will be compared to the specific and non-specific radioactivity recovered per gram of node as determined by double-label counting. In addition, nodes will be carefully examined histologically by an experienced dermal pathologist. Selected portions of tumor-involved and normal nodes will be studied by immunoperoxidase staining for the presence of antimelanoma antibody. Microautoradiographic demonstration of specific antibody localization to involved nodes will be performed. We also will produce additional monoclonal antibodies of varying isotypes and affinities to the chondroitin sulfate proteoglycan antigen of melanoma. These antibodies will be tested in nude mice bearing human melanoma xenografts, with the most promising being evaluated clinically as above and by using single-photon emission computed tomographic imaging with I-123 labeled antibody. This proposal may result in a significant improvement in our ability to accurately stage clinical Stage I and II melanomas and may allow a more selective approach to lymph node dissection. In addition, if high levels of radioactivity can selectively be developed in tumor-involved nodes, radiotherapy of nodal disease wtih radiolabeled antibody may also be possible.
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