Localization of human breast tumors grafted in nude mice with a monoclonal antibody directed against a defined cell surface antigen of human mammary epithelial cells
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A mouse monoclonal antibody (BLMRL-HMFG-Mc5) prepared against a defined cell surface antigen of human mammary epithelial cells, non-penetrating glycoprotein (NPGP), was used in imaging and distribution studies in athymic nude mice grafted with human breast tumors. Forin vivo tissue distribution studies,125I-labeled monoclonal antibody was injected into nude mice carrying simulated metastases of human tumors (breast and colon carcinomas). After 22–24 hr the amount of radioactivity per gram of tissue was 3–4 times higher in the breast tumor than in liver, brain, lung, muscle, or spleen. In contrast, colon carcinoma tissue, grafted and treated likewise, did not show higher accumulation of radioactivity relative to other tissues. At 4 days, the incorporation in breast tumors remained almost as high, while the circulating radioactive tracer and the incorporation in tissues other than breast had fallen significantly.
In tumor imaging studies, breast tumor masses as small as 4 mm in diameter were clearly localized on a whole body scan using131I-labeled BLMRL-HMFG-Mc5 antibodies with a High-Purity germanium gamma camera. Normalization of131I-distribution to that of99mTc-pertechnetate increased the specificity of this imaging methodology. The quantitative density of131I-label was 2–3 fold higher over the breast tumor than over comparable areas of the mouse. No positive localization images were obtained for similar implants of colon and lung carcinomas or melanomas after injections of131I-labeled BLMRL-HMFG-Mc5. Localization of human breast tumors in this model can be achieved with131I-labeled anti-breast epithelial monoclonal antibodies.
Key wordsbreast cancer human tumor explants imaging mammary epithelial antigen monoclonal antibody nude mice
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