Our goal is to scintigraphically detect, stage and ultimately treat ovarian carcinomas, using radiolabeled monoclonal antibodies preferentially reactive with epithelial ovarian carcinomas. Monoclonal antibodies raised against ovarian cancer, already shown capable of radiolocalizing human ovarian carcinoma xenografts in nude mice, will be further evaluated in that model. The effects of antibody dose, route of administration (intravenous as compared to intralymphatic or intraperitoneal), fragmentation, and labeling, will be evaluated to optimize antibody localization to tumor. Since ovarian carcinoma is generally a regional disease within the peritoneum and draining lymphatics, we expect this regional antibody delivery to significantly enhance tumor localization. Antibody localization will be evaluated by gamma camera scanning, tumor excision with gamma counting, immunoperoxidase staining, and microautoradiography. In parallel experiments, the specificity of existing and new monoclonals raised against ovarian cancer will be further evaluated by immunohistochemical techniques. The radiotherapeutic potential of the best monoclonals for imaging will then be evaluated in vitro using clonogenic assay techniques. The dose of radiolabeled antibody required to produce tumor kill of ovarian carcinoma lines in vitro will be determined. Based on these studies, the best antibodies will then be evaluated for radiotherapeutic potential in our nude mouse model of disseminated intraperitoneal human ovarian carcinomatosis. A variety of dosing schemes will be tested therapeutically with evaluation for the number of clonogenic ascites cells, mean survival, and cure as indices of the efficacy of radiotherapy. The monoclonal antibodies with the best localization to ovarian carcinoma xenografts in vivo, as well as showing the greatest in vitro specificity for ovarian cancer, will be evaluated in phase I imaging trials in patients with advanced ovarian cancer who are scheduled for a second debulking procedure. This will assure histologic, autoradiographic and gamma scan assessment of antibody localizaiton to tumor. This study will provide unique information regarding the optimal means of delivering radioantibody to ovarian tumors and about these tumor's sensitivity to radioantibody. This should result in a means of scintigraphically following residual ovarian carcinoma post-diagnosis and may eliminate the need for second-look diagnostic procedures. If adequate specific localization of radioantibody to ovarian cancer is achieved, then this approach may prove useful in the radioimmunotherapy of this common and lethal disease.
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