The effect of the administration route and dose of
streptavidin or
biotin on the biodistribution of radioactivity in multistep targeting was studied in nude mice bearing intraperitoneal (IP)
colon cancer xenograft. The multistep targeting included a two-step method using biotinylated antibody and radiolabeled
streptavidin and a three-step method with radiolabeled
biotin based on the two-step method. A
monoclonal antibody, MLS128, which recognizes
Tn antigen on
mucin, was biotinylated and injected intravenously (i.v.) or i.p. in nude mice bearing human
colon cancer LS180 IP xenografts for pretargeting. In the two-step method, i.p.-injected
streptavidin showed a higher
tumor uptake and
tumor-to-nontumor ratios than i.v.-injected
streptavidin regardless of administration route of pretargeting. The
tumor uptake of radiolabeled
streptavidin was increased with a high dose of biotinylated antibody pretargeting, but decreased with an increasing dose of
streptavidin. In the three-step targeting, i.p. injection also gave a higher
tumor uptake of radiolabeled
biotin than i.v. injection. In conclusion, i.p. administration of radiolabeled
streptavidin or
biotin resulted in more efficient IP
tumor targeting with the multistep methods.