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-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.
Senekowitsch-Schmidtke
R
R
Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Germany.
Schuhmacher
C
C
Becker
K F
KF
Nikula
T K
TK
Seidl
C
C
Becker
I
I
Miederer
M
M
Apostolidis
C
C
Adam
C
C
Huber
R
R
Kremmer
E
E
Fischer
K
K
Schwaiger
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics; D000918:Antibody Specificity; D001729:Bismuth / Q000627:therapeutic use*; D015820:Cadherins / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000276:immunology* / Q000493:pharmacokinetics; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000532:radiotherapy; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology / Q000532:radiotherapy*; D014018:Tissue Distribution; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015820:Cadherins; D000922:Immunotoxins; D011868:Radioisotopes; D001729:Bismuth