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

去唾液酸糖蛋白（ASCP）与肝细胞膜上的受体结合，并被肝脏特异性吸收和代谢。我们生产了在生理学上等同于ASGP的标记的新糖蛋白（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，以评价其作为扫描放射性药物的有用性：1）GHSA和ASGP受体之间的结合测定，2）在给药至门静脉后的初始循环中测量肝脏提取率，以及3）测定了正常大鼠和Galacosamine诱导的急性肝病大鼠的清除率，结合试验表明，从大鼠肝脏中获得的ASGP受体数量与<^（125）I> -GHSA浓度之间呈线性关系。用~（125）I-GHSA和肝细胞膜进行的膜分析显示了相似的结果。正常家兔门静脉给药后的初始循环中的肝提取率具有高度的剂量依赖性。外周血给药后1小时内显示，静脉注射后立即开始在肝脏中特异性蓄积正常大鼠主要经胆道系统转运至小肠，胆管结扎大鼠主要经尿液转运至小肠。以~（99）Tc> -GHSA经心脏和肝脏循环及肝脏失活释放为动力学模型，对心脏和肝脏的测量曲线进行二室分析，获得清除参数。~（99）Tc&gt; -GHSA（50-100 <mu>g/100 g体重）的给药浓度与清除率呈线性正相关，表明标记GHSA与肝ASGP受体定量结合，可作为肝功能评价的扫描放射性药物。

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.