抗癌药 NGA-DHAQ 的趋肝性及其机理研究

STUDIES ON LIVERTAXIS OF ANTINEOPLASTIC AGENT NGA DHAQ AND ITS MECHANISM

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 livertaxis of antineoplastic agent galactosylneoglycoalbumin mitoxantrone(NGA DHAQ) and its mechanism using radioactive tracer technique is studied. NGA is a synthetic ligand specific for asialoglycoprotein receptor, which existed in the mammalian liver only. NGA as a carrier of hepatic targeting agents is coupled with an antineoplastic agent DHAQ via a butanediamide bridge to form a coujugator. NGA DHAQ is labelled with 99 Tc m. The data of rabbit and chick imaging, distribution in mice and HPLC assay are obtained. The results revealed that DHAQ has remarkable livertaxis and its uptake in liver is over 65% with the feature of receptor mediated binding to hepatocytes in vivo. The results show that NGA DHAQ is a potential receptor mediated hepatic targeting antineoplastic agent.