纤维蛋白显像剂131I-YSSCREKA肽的制备及对早期血栓定位的研究

Synthesis of Fibrin-Binding Peptide 131I-YSSCREKA for Targeting Early Thrombosis

合成了一种可特异性结合纤维蛋白-纤维连接蛋白的早期血栓显像剂131I-YSSCREKA肽(酪氨酸-(D)丝氨酸-(D)丝氨酸-半胱氨酸-精氨酸-谷氨酸-赖氨酸-丙氨酸),对其标记、SPECT显像及初步生物学性能进行研究。结果表明:YSSCREKA八肽在室温下通过氯胺-T法反应5min的标记率为(77.2±1.1)%(n=3),放射化学纯度为(90.0±3.1)%(n=3),体外稳定性较好。新西兰家兔SPECT显像显示在131I-YSSCREKA肽注射后20h血栓能较清晰地显像,血栓/血放射性比值为1.36。SD大鼠生物分布实验显示:20h131IYSSCREKA肽在血栓中的摄取率为(0.19±0.06)ID%/g(n=5),血栓/肌肉及血栓/血放射性比值分别为3.80和1.90。131I-YSSCREKA肽有可能作为早期血栓的显像剂,但其在血栓中的摄取率有待于进一步提高。

To develop the radiotracer for imaging vein thrombosis,the 131I labeled octapeptide containing CREKA(Cys-Arg-Glu-Lys-Ala)sequence had been proved to bind to fibrin-fibronectin complexes in clotted plasma and was injected into animals models to investigate the targeting effect on early thrombosis.The octapeptide YSSCREKA(Tyr-(D)Ser-(D)Ser-Cys-Arg-Glu-Lys-Ala)was constructed and labeled with 131I by Ch-T method.The 131I radiolabeling yield and radiochemical purity are(77.2±1.1)%and(90.0±3.1)%(n=3)respectively.131I-YSSCREKA performs high stability in vitro at room temperature within 72h.The fresh vein thrombus is clearly visible at 20hon inferior vena cava of rabbits.The count ratio of thrombus/blood by region of interest(ROI)method is 1.36.The thrombus uptake of radiolabeled peptide at 20hpost-injection is(0.19±0.06)ID%/g(n=5).The count ratios of thrombus/muscle and thrombus/blood are 3.80and 1.90,respectively.131I-YSSCREKA is a promising tracer for early thrombosis and is worthy to be further studied to improve the thrombus uptake.