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Improved tumor detection by anti‐CEA chimeric Fab oligomers with disulfide linkages in a pancreatic‐carcinoma‐xenograft model
Author(s) -
Kamigaki Takashi,
Yamamoto Masahiro,
Ohyanagi Harumasa,
Ohya Masato,
Kono Akira,
Ohtani Wataro,
Narita Yuji,
Ohkubo Masahiro,
Ohmura Takao,
Saitoh Yoichi
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960410)66:2<261::aid-ijc21>3.0.co;2-e
Subject(s) - chemistry , monoclonal antibody , carcinoembryonic antigen , microbiology and biotechnology , disulfide bond , antibody , monomer , cancer research , biochemistry , medicine , cancer , biology , immunology , polymer , organic chemistry
We have investigated the effect of Fab oligomerization on imaging efficacy in a pancreatic‐carcinoma xenograft model in mice. Recombinant mouse/human chimeric Fab of the anti‐carcinoembryonic antigen (CEA) monoclonal antibody A10, which has been shown to react specifically with gastrointestinal cancers, was used in this study. Fab homo‐oligomers (dimers and trimers) chemically linked through disulfide bonds (S‐S Fab oligomers) were prepared by linkage of chimeric Fab with N ‐succinimidyl‐3‐(2‐pyridyldithio)‐propionate. Oligomers with S‐S bonds showed 10‐fold higher binding activity against human CEA than Fab, while the binding activity of oligomers was similar to that of F(ab′) 2 . In mice bearing pancreatic‐carcinoma xenografts, tumor uptake of S‐S oligomers was significantly greater than that of monomeric Fab, while there was no difference in tumor uptake between S‐S Fab trimers and F(ab′) 2 . S‐S oligomers showed more rapid clearance rates and uniform percolation in the tumor nodules than F(ab′) 2 . At 24 hr after injection, S‐S Fab oligomers exhibited higher tumor‐to‐normal‐tissue specificity ratios than did F(ab′) 2 . At 18 hr after injection, clear scintigraphic detection of the pancreatic‐carcinoma tumors was obtained with 123 I‐labeled S‐S Fab dimers. At 24 hr, improved tumor imaging was shown for 123 I‐labeled S‐S Fab oligomers with slightly visible uptake in normal tissues, similar to that of F(ab′) 2 . S‐S oligomers of chimeric A10 Fab may be useful as rapid diagnostic tools of pancreatic carcinomas. © 1996 Wiley‐Liss, Inc.