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Scintigraphic Detection of Overexpressed c-erbB-2 Protooncogene Products by a Class-switched Murine Anti-c-erbB-2 Protein Monoclonal Antibody

Department of Nuclear Medicine [T. S., K. E., H. S., M. K., Y. W., T. N., M. H., J. K.], Kyoto University School of Medicine, Kyoto, and Institute of Medical Science [T. A., T. Y., K. T.], Tokyo University, Tokyo, Japan

Class-switched monoclonal antibody SV2-61r recognizes the extracellular domain of c-erbB-2 protooncogene products separate from the epidermal growth factor receptor. We studied the potential of SV2-61r for evaluating the amplification of c-erbB-2 protooncogene on cancer cells, which has been reported to have prognostic value in adenocarcinoma patients. Radiolabeled SV2-61r specifically bound to various adenocarcinoma cells in addition to c-erbB-2-transfected NIH-3T3 cells (A4) with the affinity constant of 4.4 x 10⁸ M^-1. SV2-61r injected i.v. localized well to A4 cells xenografted in nude mice. Tumor uptake and localization index of radioiodinated SV2-61r were lower than those of ¹¹¹In-labeled SV2-61r, probably due to the internalization and dehalogenation of formed antibody-antigen complexes. Biodistribution and specificity of targeting were assessed by comparison among three cells, A4, lung cancer SBC-3 (c-erbB-2 weakly positive) and B-lymphoblastoid Manca cells (c-erbB-2 negative). Tumor:blood ratios, obtained 48 h after injection, were 5.63, 1.45, and 0.68, respectively, indicating the potential of ¹¹¹In-labeled SV2-61r for evaluating the amplification of c-erbB-2 protooncogene on cancer cells. Because of its close relationship with carcinogenesis and the uniform expression, c-erbB-2 protooncogene products seem to be the optimal target of imaging and therapy of adenocarcinoma patients.

¹ To whom requests for reprints should be addressed, at Department of Nuclear Medicine, Kyoto University Hospital, Shogoin, Sakyo-ku, Kyoto 606, Japan.

Received 6/18/90. Accepted 11/ 9/90.