Astatine-211 labeling of insulin: Synthesis and preliminary evaluation in vivo and in vitro
Astatine-211 labeling of insulin: Synthesis and preliminary evaluation in vivo and in vitro
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DOI：
10.1007/s10967-006-6781-8
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发表时间：
2007-02
影响因子：
1.6
通讯作者：
Ning Liu;Yuanyou Yang;L. Zan;J. Liao;Jiannan Jin
中科院分区：
文献类型：
--
作者：
Ning Liu;Yuanyou Yang;L. Zan;J. Liao;Jiannan Jin
首次尝试用α-发射体211 At标记胰岛素（一种对肿瘤具有显着亲和力的小蛋白质），是通过使用N-琥珀酰亚胺基5-（三丁基锡烷基）-3-吡啶羧酸酯（SPC）作为双功能接头的间接方法进行的，并在体外和体内评价了结合胰岛素（211 At-胰岛素）的稳定性。以5-溴烟酸为起始原料合成SPC。用这种双功能连接体标记胰岛素，标记率为30- 40%，放化纯度大于98%。室温放置24小时后，放化纯度仍大于95%，表明~（211）At-胰岛素在体外是相当稳定的。研究了~（211）At-胰岛素在NIH系小鼠体内的生物分布，~（211）At在小鼠体内迅速蓄积，30 min时最大摄取量为4.29%I. D/g，主要经肾脏排泄。更重要的是，211 At-胰岛素在一些关键器官或组织中的摄取，特别是在胰、胃、肺和脾中，远低于游离阿司他肽（211 At-）。这一结果表明~（211）At-胰岛素在体内和体外都具有相当的稳定性。
A first attempt to label insulin, a small protein with significant affinity to tumors with the α-emitter211At was performed by an indirect method using N-succinimidyl 5-(tributylstannyl)-3-pyridinecarboxylate (SPC) as a bi-functional linker, and the stability of the conjugated insulin (211At-insulin) was evaluated in vitro and in vivo. SPC was synthesized by using 5-bromonicotinic acid as the starting material. With this bi-functional linker, insulin was conjugated with211At in a labeling yield of 30–40%, with radiochemical purity of more than 98%. After 24 hours at room temperature, the radiochemical purity was still more than 95%, implying that211At-insulin is fairly stable in vitro. Biodistribution of211At-insulin was investigated in NIH strain mice.211At accumulated rapidly in the liver post injection, with the maximum uptake of 4.29%I.D/g at 30 minutes, and was mainly excreted by kidney. More importantly,211At-insulin uptake in some key organs or tissues, especially in thyriod, stomach, lung and spleen, was much less than that of free astatide (211At−). This result indicated that211At-insulin has considerable stability in vivo as well as in vitro.