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

Departments of Nuclear Medicine [R. S-S., C. Se., M. M., R. H., K. F., M. Sl.] and Surgery [C. Sch., C. Ad.], and Institute of Pathology [K-F. B., I. B.], Klinikum rechts der Isar, Technische Universität München; Institute of Molecular Immunology [E. K.]; and Institute of Pathology [K-F. B.] GSF, National Research Center for Environment and Health, München, European Commission, Institute for Transuranium Elements, Karlsruhe [T. K. N., C. Ap.], 81675 Muenchen, Germany

A monoclonal antibody (E-cadherin delta 9–1) directed against a characteristic E-cadherin 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 -emitter ²¹³Bi and tested for its binding specificity in s.c. and i.p. nude mice tumor models. After intratumoral application in s.c. tumors expressing mutant E-cadherin, the ²¹³Bi-labeled antibody was specifically retained at the injection site as shown by autoradiography. After injection into the peritoneal cavity, uptake in small i.p. tumor nodules expressing mutant E-cadherin was 17-fold higher than in tumor nodules expressing wild-type E-cadherin (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-cadherin, whereas in control cells, binding was only 18%. The selective binding of the ²¹³Bi-labeled, mutation-specific monoclonal antibody E-cadherin 9–1 suggests that it will be successful for -radioimmunotherapy of disseminated tumors after locoregional application.

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