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目的 探讨以凝血酶为靶,重组水蛭素(rH)为配基进行血栓显像的潜在价值。方法 氯胺T法制备125IrH,采用体外放射配体结合法分析rH对凝血酶纤维蛋白复合物的亲和、定量关系和时间反应动力学。亚氨基噻吩盐酸盐修饰法制备99TcmrH,进行小鼠体内分布测定及犬动、静脉血栓模型显像。结果 rH 不能直接与纤维蛋白原结合,当凝血酶与纤维蛋白形成复合物后才能与其形成三元复合物,且这种结合呈高亲和、特异和可逆性。99TcmrH 在小鼠心、脑、肝、脾、肺摄取低,肾摄取高,15 min 达(64-724±5-042) %ID/organ,血清除迅速。犬股动脉血栓于45 min 可清晰显影,靶/ 本底(T/B) 比值为1-47。静脉血栓于注药后30 min 就出现浓聚,并随时间延长血栓显影更清晰,1 h T/B比值为1-53。结论 99TcmrH 有望成为1 种新的较理想的血栓示踪剂
Objective To investigate the potential value of thrombus imaging using thrombin as target and recombinant hirudin (rH) as ligand. Methods Chloramine T 125I rH prepared by in vitro radioligand binding assay rH thrombin fibrin composite affinity, quantitative relationship and time reaction kinetics. Iminothiophene hydrochloride modified method Preparation 99Tcm rH, the distribution of the mice were measured and canine venous thrombosis model. As a result, rH can not directly bind to fibrinogen, and thrombin forms a complex with fibrin to form a ternary complex with it, and the binding is highly affinity, specificity and reversibility. 99Tcm rH in mice heart, brain, liver, spleen, lung uptake low, high renal uptake, 15 min up to (64-724 ± 5-042)% ID / organ, serum addition to rapid. Canine femoral artery thrombosis at 45 min can be clearly developed, target / background (T / B) ratio of 1-47. Thromboembolism occurred at 30 min after injection, and thrombosis became clearer with time. The 1 h T / B ratio was 1-53. Conclusion 99Tcm rH is expected to become a new kind of more ideal thrombus tracer