GLP-1受体激动剂exendin-4的放射性标记及生物分布实验研究

目的 确立131I标记胰高血糖素样肽-1(GLP-1)受体激动剂exendin-4多肽的最佳标记条件,并研究131I-exendin-4在正常小鼠体内的生物分布。 方法 131I标记exendin-4多肽采取氯胺-T方法标记,利用纸层析法计算标记产物的标记率及放化纯度,测定131I-exendin-4的体外稳定性及脂水分配系数,研究131I-exendin-4在注射后的1、3、6、12和24 h时在正常小鼠体内的分布特征,对经尾静脉注入131I-exendin-4的小鼠进行SPECT多时相显像,并观察小鼠体内放射性分布变化。 结果 exendin-4的131I标记率在85%以上,放化纯度大于97%,131I-exendin-4在人血清和生理盐水中仍保持较好的体外稳定性,131I-exendin-4的脂水分配系数为-1.002。正常小鼠静脉注入131I-exendin-4后,双肾的放射性分布明显较其他组织器官的放射性增高,1 h和12 h肾脏的每克组织百分注射剂量率(%ID/g)分别为(51.54±13.51)%ID/g和(11.61±0.94)%ID/g,胃、肺的摄取相对较高,3 h后除肾脏外的其他各脏器器官的放射性均较快下降。正常小鼠静注131I-exendin-4后的SPECT多时相显像示随着时间的延长,双肾及膀胱的放射性浓聚影增加,而其他器官未见明显放射性浓聚影分布。 结论 131I标记exendin-4的标记率较高(大于85%),体外稳定性良好,131I-exendin-4为水溶性物质,可通过泌尿系统排泄,体外分布特性比较理想。 

Radiolabeling of exendin-4 and its biodistribution in mice

Objective To establish the radiolabeling method of exendin-4, an glucagon-like peptide 1 (GLP-1) receptor agonist, with 131I and observe the biodistribution of 131I-exend in-4 in normal mice. Methods Radiolabeling of exendin-4 with 131I was performed by chloramine-T method. The labeling ratio and radiochemical purity were determined using paper chromatography and TLC. The octanol-water partition coefficient and stability in vitro in saline and normal human serum of labeled polypeptide were also determined. The biodistribution of 131I-exendin-4 in normal mice were measured at 1, 3, 6, 12, 24 h after intravenous injection. SPECT was performed in 3 male mice after injection of 131I-exendin-4 to observe the dynamic distribution of the labeled exendin-4. Results The labeling yield of 131I-exendin-4 was more than 85%. The 131I-exendin-4 had good stability in saline and normal human serum. The octanol-water partiton coefficient lg P=-1.002. The biodistribution in mice showed that 131I-exendin-4 had rapid blood clearing, and the radioactivity in kidney was obviously higher than that of other organs as indicated by their uptake of (51.54±13.51)%ID/g at 1 h and (11.61±0.94)%ID/g at 12 h, respectively. Organs such as stomach, lung, intestine and bone had transient radioactive uptake, and then after 3 h the radioactivity in those organs rapidly decreased. The radioactivity in other organs always kept at a low level. Conclusion 131I-exendin-4 can be easily labeled with a high labeling ratio with stability in vitro. It has good distribution characteristics in vivo, and is cleared mainly by renal excretion due to its hydrosolubility.