EFFECT OF ADMINISTRATION ROUTE AND DOSE OF STREPTAVIDIN OR BIOTIN ON THE TUMOR UPTAKE OF RADIOACTIVITY IN INTRAPERITONEAL TUMOR WITH MULTISTEP TARGETING

The effect of the administration route and dose of streptavidin or bio tin on the biodistribution of radioactivity in multistep targeting was studied in nude mice bearing intraperitoneal (IP) colon cancer xenogr aft. The multistep targeting included a two-step method using biotinyl ated antibody and radiolabeled streptavidin and a three-step method wi th radiolabeled biotin based on the two step method. A monoclonal anti body, MLS128, which recognizes Tn antigen on mucin, was biotinylated a nd injected intravenously (IV) or IP in nude mice bearing human colon cancer LS180 IP xenografts for pretargeting. In the two-step method, I F-injected streptavidin showed a higher tumor uptake and tumor-to-nont umor ratios than IV-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-st ep targeting, IP injection also gave a higher tumor uptake of radiolab eled biotin than IV injection. In conclusion, IP administration of rad iolabeled streptavidin or biotin resulted in more efficient IP tumor t argeting with the multistep methods. (C) 1998 Elsevier Science Inc.