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

Reingard Senekowitsch-Schmidtke, Christoph Schuhmacher, Karl Friedrich Becker, Tuomo K. Nikula, Christof Seidl, Ingrid Becker, Matthias Miederer, Christos Apostolidis, Christoph Adam, Roswitha Huber, Elisabeth Kremmer, Kathrin Fischer, Markus Schwaiger

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45 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2804-2808
Number of pages5
JournalCancer Research
Volume61
Issue number7
StatePublished - 1 Apr 2001
Externally publishedYes

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