A facile method for the labeling of proteins with zirconium isotopes
A facile method for the labeling of proteins with zirconium isotopes
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DOI：
10.1016/0969-8051(96)00020-0
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发表时间：
1996-05-01
影响因子：
3.1
通讯作者：
Herscheid, JDM
中科院分区：
文献类型：
--
作者：
Meijs, WE;Haisma, HJ;Herscheid, JDM
为了用半衰期为几天的正电子发射体标记蛋白质，已经开发了一种用锆（Zr）同位素标记蛋白质的方法。因此，双功能螯合剂Desferal（Df）通过硫醚键与白蛋白偶联。通过将这些蛋白质添加到冷冻干燥的草酸锆中，可以容易地进行预修饰蛋白质的标记。这种标记是有效的（> 90%），并在几分钟内完成。偶联物显示出高的体外稳定性。用Zr-88-柠檬酸盐、Zr-88-Df和Zr-88-标记的小鼠血清白蛋白（Zr-88，Df-MSA）进行生物分布研究，这些蛋白用不同量的螯合基团修饰。尽管发现柠檬酸锆在骨中蓄积，但Zr Df通过肾小球过滤非常快速地清除。Zr-88-Df-MSA的血液清除率与I-123标记的MSA相似。Zr-88-Df-MSA的生物分布模式与I-123-MSA的唯一不同之处在于，Zr在肝脏、肾脏和脾脏中的积累较高。骨骼中没有大量Zr-88，表明该缀合物在体内也相当稳定。
To label proteins with positron emitters with a half life in the order of days, a method has been developed to label proteins with zirconium (Zr) isotopes. Therefore, the bifunctional chelating agent desferal (Df) was coupled to albumins via a thioether bond. Labeling of the premodified proteins was easily performed by addition of these proteins to freeze dried Zr-oxalate. This labeling was efficient (> 90%) and accomplished in several minutes. The conjugates showed a high in vitro stability. Biodistribution studies were performed with Zr-88-citrate, Zr-88-Df, and Zr-88-labeled mouse serum albumin (Zr-88,Df-MSA), modified with different amounts of chelating groups. Whereas Zr citrate was found to accumulate in bone, Zr Df was cleared very fast by glomerular filtration. The Zr-88-Df-MSA showed similar blood clearance as did I-123-labeled MSA. The biodistribution pattern of Zr-88-Df-MSA differed only from I-123-MSA in that a higher accumulation of Zr in liver, kidney, and spleen was found. The absence of large amounts of Zr-88 in bone indicated that in vivo the conjugates are also reasonably stable.