Zhang M, Sakahara H, Yao Z, Saga T, Nakamoto Y, Sato N, Nakada H, Yamashina I, Konishi J
Department of Nuclear Medicine, Faculty of Medicine, Kyoto University, Japan.
Nucl Med Biol. 1997 Jan;24(1):61-4. doi: 10.1016/s0969-8051(96)00162-x.
In the present study, we examined the effect of avidin administered intravenously (i.v.) on the biodistribution of radiolabeled streptavidin in mice bearing intraperitoneal (IP) xenografts pretargeted with biotinylated antibody. Tumors were established in nude mice by IP inoculation of LS180 human colon cancer cells. Monoclonal antibody MLS128, which recognizes Tn antigen on mucin, was biotinylated and injected IP into the IP tumor-bearing mice. Radioiodinated streptavidin was administered IP or i.v. 48 h after pretargeting of biotinylated antibody. Avidin was administered i.v. 30 min prior to streptavidin injection. The localization of radioiodinated streptavidin in the tumor pretargeted with biotinylated antibody was significantly higher than that without pretargeting and that of radioiodinated MLS128 by the one-step method. Avidin administration significantly accelerated the clearance of radioiodinated streptavidin in blood and other normal tissues and increased the tumor-to-blood radioactivity ratio regardless of administration route of streptavidin. The i.v. avidin chase improved tumor localization of radiolabeled streptavidin in the IP xenografts pretargeted with biotinylated antibody.
在本研究中,我们检测了静脉注射抗生物素蛋白对荷有经生物素化抗体预靶向的腹腔内(IP)异种移植瘤小鼠体内放射性标记的链霉亲和素生物分布的影响。通过腹腔接种LS180人结肠癌细胞在裸鼠体内建立肿瘤。识别粘蛋白上Tn抗原的单克隆抗体MLS128经生物素化后腹腔注射到荷IP肿瘤的小鼠体内。在生物素化抗体预靶向48小时后,腹腔或静脉注射放射性碘化链霉亲和素。在注射链霉亲和素前30分钟静脉注射抗生物素蛋白。经生物素化抗体预靶向的肿瘤中放射性碘化链霉亲和素的定位显著高于未预靶向的情况以及一步法放射性碘化MLS128的定位。无论链霉亲和素的给药途径如何,注射抗生物素蛋白均显著加速了放射性碘化链霉亲和素在血液和其他正常组织中的清除,并提高了肿瘤与血液的放射性比值。静脉注射抗生物素蛋白进行追踪可改善经生物素化抗体预靶向的IP异种移植瘤中放射性标记链霉亲和素的肿瘤定位。