中文摘要：

目的尝试合成肝脏靶向对比剂乳糖基白蛋白超顺磁氧化铁（Gal-BSA-SPIO），探讨Gal-BSA-SPIO对肝癌的检出及其诊断价值。材料和方法采用还原胺法合成Gal-BSA。Gal-BSA与SPIO混合后超声振荡。建立20只兔的VX2肝癌模型，随机分为SPIO组和Gal-BSA-SPIO组，行MR平扫及增强。测定肝脏及肿瘤的T2值。对13例人肝脏标本（肝癌6例、肝硬化4例、正常肝组织3例）Gal-BSA-SPIO孵育后，Perl’s染色，观察去唾液酸糖蛋白（ASG）受体分布。统计学方法：对增强前后各组的T2值进行t检验。结果Gal—BSA-SPIO平均粒径34．4nm。20只兔VX2肿瘤直径3～12mm，T1WI肝实质呈中等信号，肿瘤呈低信号，T2M肝实质低信号，病灶为略高信号；GRET2＊WI肝实质中等信号，肿瘤略高信号。增强扫描，SPIO组T2WI肝实质信号轻中度下降，与肿瘤对比提高；Gal-BSA-SPIO组T2WI肝实质信号显著下降，肿瘤呈明亮的“灯泡征”。正常肝脏的SPIO组和Gal-BSA—SPIO组增强后T2值明显下降，与增强前有显著性差异。肿瘤的SPIO组和Gal-BSA-SPIO组增强后T2值无明显下降，与增强前无显著性差异。组织学检查SPIO组，Kupffer细胞内见蓝染的铁颗粒；Gal-BSA-SPIO组．肝细胞内见较多的蓝染的铁颗粒，两组的肿瘤内未见蓝染的铁颗粒。Gal-BSA-SPIO孵育后，正常肝组织可见大量蓝染色，肝硬化及癌旁肝硬化组织均可见蓝染色；肝细胞癌罕见蓝染色。结论Gal-BSA-SPIO可以与肝细胞膜的ASG受体可特异性结合，通过受体介导的特异性对肝脏产生负向增强作用。明显提高肿瘤对比噪声比。

英文摘要：

Objective To synthesize Gal-BSA-SPIO as the magnetic resonance imaging （MRI） contrast agent targeting asialoglycoprotein （ASG） receptors in the liver and observe its role in MRI detection ofhepatocellular carcinomas （HCCs）. Methods Gal-BSA was synthesized by means of reductive amination and mixed with SPIO in ice bath to prepare Gal-BSA-SPIO complex. Twenty rabbits bearing VX2 liver tumor underwent MR/ enhanced by SPIO （n=10）. and Gal-BSA-SPIO （n=10）, and the T2 values of the liver and tumor before and after the contrast imaging were measured. Fresh human normal hepatic tissues （n=3）, cirrhotic tissues （n=4） and HCC tissues （n=6） were obtained and incubated with Gal-BSA-SPIO followed by Perl＇s Prussian blue staining to observe the distribution of ASG receptors. Results The size of the Gal-BSA-SPIO particles was 34.4 nm. The 20 rabbits bearing VX2 tumor, with tumor size ranging from 3 mm to 12 mm, showed isointense signal in the liver and hypointense signal in the tumor on TIWI, and isointense signal in the liver and slightly hyperintense signal in the tumor on GRE T2＊WI. The signal intensity of the liver decreased slightly or moderately after administration of SPIO in the rabbits, and administration Gal-BSA-SPIO resulted in obvious reduction in the signal intensity of the liver. The signal intensities of the tumors did not exhibit obvious changes after the administration of SPIO or Gal-BSA-SPIO. Histological examination revealed numerous blue iron deposits in the Kupffer cells in SPIO group and in the hepatocytes in Gal-BSA-SPIO group, but not in the tumors in either of the groups. The human liver specimens incubated with Gal-BSA-SPIO contained numerous blue iron deposits in the hepatocyte cytoplasm and cell membrane in normal liver tissue, but the deposits were reduced in the cirrhotic tissue and almost absent in the HCC tissue. Conclusion Gal-BSA-SPIO can specifically bind to ASG receptors on hepatocyte membrane to improve the tumor-liver contrast-to-noise ratio.