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利用放射性核素示踪法研究抗癌药半乳糖新糖白蛋白-米托蒽醌(NGA-DHAQ)的趋肝性及其机理,探讨其作为受体介导肝靶向抗癌药的可能性。以哺乳动物肝细胞无唾液酸糖蛋白受体的特异性配体NGA为载体,通过丁二酰胺桥与抗癌药DHAQ偶联,制备了肝靶向抗癌药NGA-DHAQ;采用99Tcm标记后,进行家兔和鸡显像、小鼠体内分布实验,并对静注NGA-DHAQ小鼠的血、肝样品进行HPLC检测。核素示踪研究表明,NGA-DHAQ有高度的趋肝性和受体介导结合特性,肝摄取峰值达65%。HPLC检测证实NGA-DHAQ在血中十分稳定,NGA能有效地将其导向肝脏,肝、血药时曲线下面积之比达66.49,验证了核素示踪研究的结果。因此,NGA-DHAQ作为受体介导肝靶向抗癌药具有进一步研究的价值。
The use of radionuclide tracer method to study the anti-cancer drug galactose neoglycoprotein-mitoxantrone (NGA-DHAQ) and its mechanism of hepatotoxicity, as a receptor-mediated liver targeting anticancer drugs may Sex. NGA-DHAQ, a liver-targeted anticancer drug, was prepared by coupling succinic amide bridge with anticancer drug DHAQ using NGA as a specific ligand of mammalian hepatocyte asialoglycoprotein receptor. After labeled with 99Tcm , Imaging of rabbits and chickens, in vivo distribution in mice, and HPLC detection of blood and liver samples of intravenous NGA-DHAQ mice. Nuclide tracing studies have shown that NGA-DHAQ has a high degree of hepatotrophic and receptor-mediated binding properties with a peak hepatic uptake of 65%. The results of HPLC showed that NGA-DHAQ was stable in blood and NGA was able to effectively target liver, liver and plasma when the area under the curve reached 66.49, which verified the results of nuclide tracing study. Therefore, NGA-DHAQ as a receptor-mediated liver-targeting anti-cancer drugs have further research value.