The development of a new liver function test using the labeled asialoglycoprotein.

asialalglycoprotein （ASCP）与肝细胞膜上的受体结合，被肝脏特异性吸收并代谢。我们生产了与ASGP生理等效的标记新糖蛋白（GHSA），并使用以下方法定量检查其被肝脏摄取是否与剂量相关，以评估其作为扫描放射性药物的有效性：1) GHSA与ASGP受体结合测定，2)门静脉给药后初始循环肝脏提取率测定，3)正常大鼠和半乳糖胺急性肝病大鼠清除率测定。结合实验显示，<^(125)I b> -GHSA浓度与从大鼠肝脏中获得的ASGP受体数量呈线性关系。使用<^(125)ib> -GHSA和肝细胞膜进行的膜试验显示了类似的结果。正常家兔门静脉给药后初始循环肝脏提取率呈高度剂量依赖性。<^(99m)Tc> -GHSA在给药后2小时内进入外周血连续显像显示，静脉注射后立即开始在肝脏特异性假设，随后主要通过胆道系统进入正常大鼠的小肠，主要进入胆管结扎大鼠的尿液。以<^(99m)Tc> -GHSA为动态模型，采用其经心、肝循环及肝失活释放，对心、肝测量曲线进行双室分析，得到清除率参数。给药浓度<^(99m)Tc> -GHSA （50-100 <mu >g /100g体重）与清除率呈线性正相关。这些结果表明，标记的GHSA定量结合肝脏ASGP受体，是一种有用的扫描放射性药物，用于评估肝功能。

Asialoglycoprotein (ASCP) binds to the receptors on the liver cell membrane, and is specifically taken up by the liver and metabolized. We produced labeled neoglycoprotein (GHSA) that is physiologically equivalent to ASGP, and quantitatively examined whether its uptake by the liver is dose-related using the following methods in order to evaluate its usefulness as s scanning radiopharmaceutical: 1) binding assay between GHSA and ASGP receptors, 2) measurement of the liver extraction ratio in the initial circulation following administration into the portal vein and 3) measurement of clearance in normal rats and rats with galacosamine-induced acute liver disorder.The binding assay showed a linear relationship between the concentration of <^(125)I> -GHSA and the amount of ASGP receptors obtaind from the rat liver. A membrane assay using <^(125)I> -GHSA and the liver cell membrane revealed similer results.The liver extraction ratio in the initial circulation following the administration into the portal vein of normal rabbits was highly dose-dependent.Serial imaging of <^(99m)Tc> -GHSA during two-hour period after administration into the peripheral blood showed specific assumulation in the liver beginning immediately after the intravenous injection and subsequent transport mainly via the biliary system into the small intestine in the normal rat and mainly into the urine in the bile duct ligated rat.As a dynamic model of <^(99m)Tc> -GHSA,its circulation through the heart and liver and inactivated release from the liver was used, and two-compartment analysis was made on measurement curves in the heart and liver obtain clearance parametres. The concentration of administered <^(99m)Tc> -GHSA (50-100 <mu> g/100g body weight) showed a positive linear relationship with clearance.These results show that labeled GHSA binds quantitatively to liver ASGP receptors and is useful as a scanning radiopharmaceutical in evaluating liver functions.