Highly specific tumor binding of a ²¹³bi-labeled monoclonal antibody against mutant E-cadherin suggests its usefulness for locoregional α-radioimmunotherapy of diffuse-type gastric cancer

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 α-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 δ 9-1 suggests that it will be successful for α-radioimmunotherapy of disseminated tumors after locoregional application.