Evaluation of an anti-carcinoembryonic monoclonal antibody suitable for immunoscintigraphy.
An anti-carcinoembryonic antigen (CEA) monoclonal antibody (mAb 6D1. 1) was evaluated in vitro and in vivo to determine its suitability as a tracer for immunoscintigraphy of colorectal carcinomas. Determination of mAb affinity for CEA showed a constant of association of 0.63 +/- 0.11 x 10(9) M-1. Binding of technetium-99m (99mTc)-6D1.1, labeled by a direct method, to human cultured lineages was highly specific. Binding to only CEA-positive LS-174T cells resulted in a saturable curve inhibited by pre-incubation with unlabeled mAb. No binding at all was observed for the human lineages MeWo (melanoma) or ZR75-30 (breast carcinoma), neither of them expressing CEA cells. Intravenous injection of 99mTc-6D1.1 into nude mice xenografted with human LS-174T tumors resulted in planar images of excellent quality. Localization of an irrelevant mAb labeled with either 99mTc or iodine-125 was never observed in tumor masses. Biodistribution studies on excised tumoral tissue showed retention of 28.48% of the injected dose per gram of LS-174T tumor. The tumor-to-blood ratio was 3.46. The same analysis performed on the other three human xenografted tumors studied demonstrated that only the CEA-producing HT-29 (colorectal adenocarcinoma) retained 99mTc-6D1.1 while the other two (ZR75-30 and MeWo) did not. These data demonstrate that this mAb is an adequate tool for targeting CEA-expressing tumors in experimental models.
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Instituto Ludwig de Pesquisa sobre o Câncer, São Paulo, SP, Brasil.
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002277:Carcinoma / Q000000981:diagnostic imaging*; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging*; D051379:Mice; D011877:Radionuclide Imaging; D013667:Technetium
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D013667:Technetium