This center has over 10 years experience in evaluating monoclonal antibodies (mAbs) in the diagnosis and treatment of cancer. The Nuclear Medicine Service has overseen all studies involving radiolabeled mAbs, and has developed and assessed various kinetic dosimetric models. We have evaluated two radiolabeled mAbs against ovarian cancer and refined our evaluation of anti-ovarian cancer antibodies, as well as the utility of intraoperative radiation detector in radioimmunodetection. The development of humanized antibodies has been a major advance, the lack of significant immunogenicity permitting multiple infusions in the same patient. This project seeks to evaluate four hypotheses: 1) That antibodies reacting against homogeneously expressed antigens expressed by the majority of ovarian cancers will show improved targeting of disease, and are candidates for selective delivery of therapeutic agents to ovarian cancer. 2) That radionuclides with optimal physical characteristics labeled to anti-ovarian cancer antibodies will improve the preoperative and intraoperative detection of ovarian cancer. 3) That radioimmunodetection using intraoperative beta-minus and gamma detection devices will allow improved detection of ovarian cancer deposits. 4) That radiolabeled monoclonal antibody therapy will be beneficial in the treatment of ovarian cancer, especially minimal residual disease. The pharmacokinetics and tumor localization of F(ab)2 fragments of monoclonal antibody Mx35 will be evaluated. New antibodies against homogeneously expressed antigen (Lewis, folate-binding protein, and MUC-1) have been developed in the laboratories of Drs. Old and Lloyd, which interact closely with the Nuclear Medicine Service. The pharmacokinetics and tumor targeting of radiolabeled fragments, and humanized antibodies against the folate-binding protein, the Lewis antigen, and mucin antigens, will be studied to determine their utility in radioimmuno- detection and therapy. Various radionuclides labeled with optimal biologic doses of antibodies will be studied to evaluate the optimum radionuclide/antibody combination for radioimmuno-detection and/or therapy; and the utility in radioimmunodetection of various hand-held intraoperative radioactivity probes and cameras developed in this institution will be assessed. Finally, we will evaluated the biologic and therapeutic effect(s) of radioimmunotherapy for its eventual use in patients with minimal residual disease.
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