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.
Cancer Res
; 61(7): 2804-8, 2001 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-11306447
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 alpha-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 delta 9-1 suggests that it will be successful for alpha-radioimmunotherapy of disseminated tumors after locoregional application.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Radioisótopos
/
Neoplasias Gástricas
/
Bismuto
/
Caderinas
/
Imunotoxinas
/
Anticorpos Monoclonais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Alemanha