Labeling of low-density lipoproteins using the 18F-labeled thiol-reactive N-[6-(4-[18F]fluorobenzylidene)aminooxyhexyl]maleimide

The novel thiol-group-selective bifunctional F-18-labeling agent N-[6-(4-[F-18]fluoro-benzylidene)aminooxyhexyl]maleimide ([F-18]FBAM) has been developed. The bifunctional labeling precursor N-(6-aminoxyhexyl)maleimide containing a thiol-reactive maleimide group and a carbonyl-group-reactive aminooxy group was prepared in only three steps in a total chemical yield of 59%. Subsequent radiolabeling with 4-[F-18]fluorobenzaldehyde gave the bifunctional F-18-labeling agent [F-18]FBAM in a radiochemical yield of 29%. In a typical experiment, 3.88 GBq of [F-18]fluoride could be converted into 723 MBq of [F-18]FBAM within 69 min. Conjugation of [F-18]FBAM with thiol groups was exemplified with the cystein-containing tripeptide glutathione and with various apolipoproteins of human low-density lipoprotein (LDL) subfractions. The latter was evaluated with respect to the uptake of [F-18]FBAM-LDL subtractions in human hepatoma cells (HepG2) in vitro. In vivo biodistribution studies in rats revealed high stability for [F-18]FBAM-LDL subtractions. Moreover, the metabolic fate of [F-18]FBAM-LDL subtractions in vivo was delineated by dynamic positron emission tomography studies using a dedicated small animal tomograph. Data were compared to former studies that used the NH2-reactive F-18-labeling agent N-succinimidyl-4-[F-18]fluorobenzoate. The compound [F-18]FBAM can be considered as an excellent prosthetic group for the selective and mild F-18 labeling of thiol-group-containing biomolecules suitable for subsequent investigations in vitro and in vivo. (c) 2007 Elsevier Inc. All rights reserved.