We investigated the effect of stabilized Fab oligomerization by
disuccinimidyl suberate on
tumor uptake in a
pancreatic carcinoma xenograft model in nude mice. Recombinant mouse/human chimeric Fab of the anti-
carcinoembryonic antigen (CEA)
monoclonal antibody A10, which was previously shown to react specifically with
gastrointestinal cancers was used in this study. Fab homo-oligomers (dimers and trimers) chemically linked with
ethylene bonds (C-C oligomers) were produced by linkage of chimeric Fab. Oligomers with C-C bonds had similar immunoreactivity against human CEA to parental Fab monomer. In biodistribution studies in animals bearing
pancreatic carcinoma xenografts, at 12 and 24 h after infusion, C-C oligomers showed significantly greater uptakes in
tumors than Fab or F(ab')2 but lower than
IgG. However, oligomers with C-C bonds maintained higher
tumor to normal tissue specificity ratios than
IgG 24 h post-infusion. In conclusion,
tumor uptake was enhanced by Fab oligomerization with C-C bonds, compared to Fab or F(ab')2, perhaps due to the larger molecular size. It was also shown that C-C Fab oligomers could have a potency to deliver high-dose
radionuclides with reduced radio-uptakes in normal tissues for the
radioimmunotherapy of gastrointestinal
carcinomas.