IMPROVED INTRATUMORAL PENETRATION OF RADIOLABELED STREPTAVIDIN IN INTRAPERITONEAL TUMORS PRETARGETED WITH BIOTINYLATED ANTIBODY

Inefficient intratumoral penetration of pharmaceuticals is one of the major limiting factors against effective tumor-targeting therapy, This study investigated the effect of the distribution pattern of the bind ing site in tumors on the penetration of target material. Methods: In the first experiment, radiolabeled biotinylated monoclonal antibody, M LS128, was injected intraperitoneally or intravenously into nude mice bearing intraperitoneal human colon cancer xenografts, In the second e xperiment, radiolabeled streptavidin was injected intraperitoneally in the tumor-bearing mice after the pretargeting with the unlabeled biot inylated antibody. Intratumoral distribution of radioactivity was exam ined with quantitative autoradiography. Results: There was no differen ce in the biodistribution of biotinylated antibody between intraperito neal and intravenous administrations, but autoradiography showed a hig her uptake in the margin and a lower uptake in the center of radioacti vity in tumor nodules with intraperitoneal injection and a more unifor m intratumoral radioactivity distribution with intravenous injection, In the two-step method, radioactivity in a low dose of streptavidin wi th intraperitoneal pretargeting primarily localized at the tumor margi n, By increasing the dose, streptavidin penetrated more deeply, In tum ors with intravenous pretargeting, a more uniform intratumoral distrib ution of streptavidin was obtained. The biodistribution of radiolabele d streptavidin was the same between different pretargeting routes, Con clusion: The better intratumoral penetration of radiolabeled streptavi din after intravenous pretargeting than intraperitoneal pretargeting w ith biotinylated antibody may be the result of different intratumoral distribution of the binding site for the radiolabel.