Meijs W E, Haisma H J, Van der Schors R, Wijbrandts R, Van den Oever K, Klok R P, Pinedo H M, Herscheid J D
RadioNuclideCentre, Free University, Amsterdam, The Netherlands.
Nucl Med Biol. 1996 May;23(4):439-48. doi: 10.1016/0969-8051(96)00020-0.
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 88Zr-citrate, 88Zr-Df, and 88Zr-labeled mouse serum albumin (88Zr-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 88Zr-Df-MSA showed similar blood clearance as did 123I-labeled MSA. The biodistribution pattern of 88Zr-Df-MSA differed only from 123I-MSA in that a higher accumulation of Zr in liver, kidney, and spleen was found. The absence of large amounts of 88Zr in bone indicated that in vivo the conjugates are also reasonably stable.
为了用半衰期在数天左右的正电子发射体标记蛋白质，已开发出一种用锆（Zr）同位素标记蛋白质的方法。因此，双功能螯合剂去铁胺（Df）通过硫醚键与白蛋白偶联。将这些预修饰的蛋白质添加到冻干的草酸锆中，即可轻松实现对其标记。这种标记效率很高（>90%），且在几分钟内即可完成。偶联物在体外表现出很高的稳定性。用不同数量螯合基团修饰的88Zr-柠檬酸盐、88Zr-Df和88Zr标记的小鼠血清白蛋白（88Zr-Df-MSA）进行了生物分布研究。结果发现，Zr-柠檬酸盐在骨骼中蓄积，而Zr-Df通过肾小球滤过很快被清除。88Zr-Df-MSA的血液清除情况与123I标记的MSA相似。88Zr-Df-MSA的生物分布模式与123I-MSA的不同之处仅在于，在肝脏、肾脏和脾脏中发现Zr的蓄积量更高。骨骼中没有大量的88Zr，这表明在体内偶联物也相当稳定。
