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  • Highly Specific Tumor Binding of a 213Bi-labeled Monoclonal Antibody against Mutant E-Cadherin Suggests Its Usefulness for Locoregional Alpha-Radioimmunotherapy of Diffuse-Type Gastric Cancer


A monoclonal antibody (E-cadherin delta 9-1) directed against a characteristic E-cadherln mutation (in-frame deletion of exon 9), found in diffuse-type gastric cancer but not in any normal tissue, was conjugated with the high linear energy transfer a-emitter 213Bi and tested for its binding specificity in s.c. and i.p. nude mice tumor models. After Intra-tumoral application in s.c. tumors expressing mutant E-cadberln, the 2l3Bi-labeled antibody was specifically retained at tile injection site as shown by autoradiography. After injection into tile peritoneal cavity, uptake in small i.p. tumor nodules expressing mutant E-cadherln was 17-fold higher than in tumor nodules expressing wild-type E-cadherln (62% injected dose/g versus 3.7% injected dose/g). 78% of the total activity in the ascites fluid was bound to free tumor cells expressing mutant E-cadberln, whereas in control cells, binding was only 18%. The selective binding of tile 213Bi-labeled, mutation-specific monoclonal antibody E-cadberln delta 9-1 suggests that it will be successful for alpha-radioim-munotilerapy of disseminated tumors after locoregional application.

Additional information

Authors: SENEKOWITSCH-SCHMIDT (ET AL), Technical University Munchen (DE);NIKULA T.K, JRC-Institute for Transuranium Elements, Karlsruhe (DE);APOSTOLIDIS C, JRC-Institute for Transuranium Elements, Karlsruhe (DE)
Bibliographic Reference: An article published in: Cancer Research 61 (2001), pp.2804-2808
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