【摘要】 文章涉及一种凝血酶(Th)的有效抑制剂——重组水蛭素(rHHV2),评价其作为血栓形成诊断工具的可能性。采用氯胺-T法制备了I-rHHV2和I-Th,标记率分别为86.64%和62.20%,125125放化纯分别为89.70%和91.22%,比放射性分别为22.4和94.3TBq/mmol。于预包被纤维蛋白原或Th的塑料小珠上进行放射性竞争分析显示,Th-纤维蛋白复合物的形成不影响rHHV2与其上的Th结合;在rHHV2,Th和纤维蛋白原形成的三元复合物中,其分子比为14141。99mTc-rHHV2的制备采用亚氨基噻吩盐酸盐修饰法,标记率为90.81%,放化纯为93.9%,比放射性为2.30TBq/mmol,犬和兔血栓模型显像用量为30μg/kg。SPECT显像分析表明血栓清晰可见,且动静脉血栓显像结果差异明显。动脉血栓在给药后45min显像清晰,随后影像逐渐减退;静脉血栓在给药后30min开始显像,并随时间的延长影像趋于清晰。小鼠体内分布证明rHHV2主要从泌尿系统排泄。这些结果说明靶向Th-纤维蛋白复合物中Th的99mTc-rHHV2可望成为一种新的血栓显像剂。更多还原

【Abstract】 The purpose of this study is to evaluate the effect of recombinant hirudin HV2 (rHHV2) as a thrombus imaging agent. 125I-rHHV2 and 125I-Th were prepared with Chloramine method, the labeling rate were 86.64% and 62.20%, with the radioactive purity of 89.70% and 91.22%, with the specific activity of 22.4 TBq/mmol and 94.43 TBq/mmol respectively. The competitive radioassays showed that the Th-fibrin complex formation did not affect the ability of rHHV2 binding with Th. In the complex, the molecular binding ratio of rHHV2 to Th and fibrinogen was 14:14:1. 99mTc-rHHV2 was prepared by 2-iminothiolane modified method, the labeled rate was 94%, with the radioactive purity of 93.90%, with the specific activity of 2.30 TBq/mmol. It was used to image fresh thrombi on arteries and veins of dog or rabbit (30 μg/kg). In SPECT images, all thrombin were clearly visible, arterial thrombosis imaging can be seen clearly within 45 min after injection and fade away slowly, venous thrombosis imaging also can be seen within 30 min after injection and quantitative imaging ratios between the thrombus and opposite vessel increased following the time. Biodistribution studies in mouse demonstrated that rHHV2 was excreted from kidneys. These data indicate that Th in Th-fibrin complex could be a potent target for diagnosis of thrombus and 99m Tc-rHHV2 could be a new thrombotic imaging agent.更多还原