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A human/mouse chimeric monoclonal antibody against CA125 for radioimmunoimaging of ovarian cancer
Authors:Hisataka Kobavashi  Harumi Sakahara  Tsuneo Saga  Makoto Hosono  Makoto Shirato  Hidetoshi Kanda  Kaichiro Ishibashi  Takeshi Watanabe  Keigo Endo  Isamu Ishiwata  Junji Konishi
Affiliation:(1) Department of Nuclear Medicine, Kyoto University Faculty of Medicine, 54, Kawahara-cho, Shogoin, Sakyo-ku, 606 Kyoto, Japan;(2) Eiken Chemical Co. Ltd., Tokyo, Japan;(3) Department of Molecular Immunology, Medical Institute of Bioregulation, Kyusyu University, Fukuoka, Japan;(4) Department of Nuclear Medicine, Gunma University School of Medicine, Gunma, Japan;(5) Ishiwata Obstetrics and Gynecology Hospital, Mito, Ibaragi, Japan
Abstract:Murine monoclonal antibody 196-14 recognizes the ovarian-cancer-associated antigen CA 125, but the epitope it recognizes is different from that of monoclonal antibody OC125. We developed a human/mouse chimeric 196-14 using the variable regions of the murine 196-14 and human heavy-chain (gammal) and light-chain (kappa) constant regions. Cell binding and competitive inhibition assays using chimeric 196-14 labeled with125I,111In or99mTc demonstrated that the in vitro immunoreactivity of the chimeric antibody was identical to that of the parental murine monoclonal antibody. However, in mice bearing human ovarian cancer xenografts, the clearance from blood was faster and absolute levels of accumulation in the tumor were lower for the125I-labeled or99mTc-labeled chimeric antibody than for the murine antibody labeled with the corresponding radionuclides. The tumor-to-blood radioactivity ratio was not significantly different between the chimeric antibody and the murine antibody, regardless of the radionuclide used for labeling. Chimeric antibody 196-14 labeled with131I,111In or99mTc is promising for the radioimmunoimaging of ovarian cancer.
Keywords:Monoclonal antibody  Immunodetection  CA125  Ovarian cancer
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