title: A facile method for the labeling of proteins with zirconium isotopes.
abstract: 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.
authors.affiliation: RadioNuclideCentre, Free University, Amsterdam, The Netherlands.
authors.forename: W E
authors.initials: WE
authors.lastname: Meijs
authors.forename: H J
authors.initials: HJ
authors.lastname: Haisma
authors.forename: R
authors.initials: R
authors.lastname: Van der Schors
authors.forename: R
authors.initials: R
authors.lastname: Wijbrandts
authors.forename: K
authors.initials: K
authors.lastname: Van den Oever
authors.forename: R P
authors.initials: RP
authors.lastname: Klok
authors.forename: H M
authors.initials: HM
authors.lastname: Pinedo
authors.forename: J D
authors.initials: JD
authors.lastname: Herscheid
mesh_terms: D000818:Animals; D002417:Cattle; D002614:Chelating Agents / Q000737:chemistry; D003676:Deferoxamine / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D005260:Female; D007553:Isotope Labeling / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D011868:Radioisotopes; D012710:Serum Albumin, Bovine / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015040:Zirconium / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D002614:Chelating Agents; D011868:Radioisotopes; D012710:Serum Albumin, Bovine; D015040:Zirconium; D003676:Deferoxamine