The objective continues to be to develop techniques which will allow the use of radiolabeled monoclonal antibodies in combination with nuclear medicine imaging for the in vivo detection and localization of malignant disease. The ultimate goal is one of utilizing these reagents to deliver therapeutic doses of radionuclides for the treatment of malignancies. These studies should have applicability to a wide variety of tumor systems. However, most of our work will continue to be conducted in the germ cell tumor system (testicular nonseminomatous tumors and female choriocarcinomas). We plan to continue intravenous patient imaging studies with 5F9.3, a monoclonal antibody reactive with an antigen expressed on both female and male germ cell tumors. In females, we will expand our early successful experience in the detection of occult choriocarcinomas (in patients with a history of this tumor presenting only with a rising HCG) by using intravenous radioantibody delivery and our recently-developed computer-aided cinematic image display method. In males, with non-seminomatous testicular cancers, we plan to begin studies of the efficacy of the intralymphtic route of radioantibody delivery in the detection of occult foci of retroperitneal nodal disease. This method, shown capable of detecting very small foci of disease in our animal model, wll be evaluated initially with I-131 antibody. However, in the 3rd-5th grant years I-123 radioantibody SPECT will also be studied, with images evaluated by comparison to CT, lymphangiography, and surgical resection with specimen counting histology, immunoperoxidase staining and autoradiography. If this diagnostic approach is successful, it will lead to more rational decisions on which patients should have lymph node dissections and on when chemotherapy can be discontinued. Additional monoclonal antibodies we have developed which are strongly reactive with testicular tumors, such as UM149 and 8D3, will simultaneously be evaluated in the animal model system for tumor localization. Several new high affinity monoclonal antibodies will be produced, selecting for reactivity with the antigen recognized by the 5F9.3 and evaluated as above. Radioantibodies developing the highest tumor/non-tumor ratios will be evaluated for radiotherapeutic potential in a nude mouse model. If these animal therapeutic results are promising, then therapy in man will be undertaken. The methods developed in this work should have a significant impact on the diagnosis and therapy of germ cell tumors and may be more broadly applicable to providing new capabilities in the detection and therapy of cancer.
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