A FACILE METHOD FOR THE LABELING OF PROTEINS WITH ZIRCONIUM ISOTOPES

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 prem odified proteins was easily performed by addition of these proteins to freeze dried Zr-oxalate. This labeling was efficient (> 90%) and acco mplished in several minutes. The conjugates showed a high in vitro sta bility. 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 fou nd to accumulate in bone, Zr Df was cleared very fast by glomerular fi ltration. The Zr-88-Df-MSA showed similar blood clearance as did I-123 -labeled MSA. The biodistribution pattern of Zr-88-Df-MSA differed onl y 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 i ndicated that in vivo the conjugates are also reasonably stable.