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.
Bibliographic Reference: An article published in: Cancer Research 61 (2001), pp.2804-2808
Record Number: 200013544 / Last updated on: 2001-07-25
Original language: en
Available languages: en