肝细胞受体显像剂99mTc-GSA的制备及其药盒化

通过DTPA环酐，将双功能连接剂引入人血白蛋白（HSA）分子；再通过合成2-亚氨基-2-甲氧基乙基-1-硫代-β-D-半乳吡喃糖苷，与DTPA-HSA反应，引入硫代半乳糖残基，得到GSA。以氯化亚锡为还原剂，通过标记条件的摸索成功制备了标记率大于96%的标记配合物99mTc-GSA。为方便该药物的临床研究以及应用推广，进一步研制了无菌的GSA一步法冻干药盒，并对湿法以及冻干法制备的该标记配合物进行了比较。在正常小鼠以及肝损伤模型中的分布试验表明，99mTc-GSA在正常小鼠肝脏中有较高的摄取，在30min时，肝脏摄取仍大于70%ID•g-1，且具有饱和性；在肝损伤模型中肝摄取值低于正常小鼠（P=0.0324）。药盒法标记所得生物数据与湿法标记相当。所得GSA一步法冻干药盒标记简单可靠，有优良的生物性能，可提供临床进一步研究、应用。

The Preparation of 99Tcm-GSA and Its Instant Lyophilized Kit for Hepatic Receptor Imaging

The ligand GSA (DTPA-galactosyl-human serum albumin) was synthesized by first introducing bifunctional chelator DTPA (diethylenetriamine pentaacetic acid) to human serum albumin (HSA) via DTPA anhydride, and then coupling galactosyl units (2-imino-2-methoxyethyl-thio-galactose) to DTPA-HSA. GSA was labeled with technetium-99m by using SnCl2 as reductant and the labeling conditions of 99mTc-GSA were optimized. Lyophilized kit of GSA was also developed for instant preparing of 99mTc-GSA. Technetium labeling yields in excess of 96% by using both of liquid and lyophilized labeling methods. Biodistribution of 99mTc-GSA was investigated in both normal and liver-injury model mice. 99mTc-GSA showed high liver uptake in normal mice (> 70%ID•g-1 at 30 min after injection). The liver uptake in liver-injury model mice is lower than that of in normal mice (P=0.0324). The promising biological properties of 99mTc-GSA combined with the development of reliable and instant lyophilized GSA kit afford the opportunity of liver receptor imaging for routine clinical assessment of hepatocyte function.