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

Abstract

The novel thiol-group-selective bifunctional 18F-labeling agent N-[6-(4-[18F]fluoro-benzylidene)aminooxyhexyl]maleimide ([18F]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-[18F]fluorobenzaldehyde gave the bifunctional 18F-labeling agent [18F]FBAM in a radiochemical yield of 29%. In a typical experiment, 3.88 GBq of [18F]fluoride could be converted into 723 MBq of [18F]FBAM within 69 min. Conjugation of [18F]FBAM with thiol groups was exemplified with the cysteine-containing tripeptide glutathione and with various apolipoproteins of human low-density lipoprotein (LDL) subfractions. The latter was evaluated with respect to the uptake of [18F]FBAM-LDL subfractions in human hepatoma cells (HepG2) in vitro. In vivo biodistribution studies in rats revealed high stability for [18F]FBAM-LDL subfractions. Moreover, the metabolic fate of [18F]FBAM-LDL subfractions 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 18F-labeling agent N-succinimidyl-4-[18F]fluorobenzoate. The compound [18F]FBAM can be considered as an excellent prosthetic group for the selective and mild 18F labeling of thiol-group-containing biomolecules suitable for subsequent investigations in vitro and in vivo.

• Authors: Mathias Berndt, Jens Pietzsch, Frank Wuest
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 34 Issue 1 Pg. 5-15 (Jan 2007) ISSN: 0969-8051 [Print] United States
• PMID: 17210457 (Publication Type: Journal Article)

Chemical References

• Lipoproteins, LDL
• Maleimides
• N-(6-(4-fluorobenzylidene)aminooxyhexyl)maleimide
• Radiopharmaceuticals

Topics

• Animals
• Carcinoma, Hepatocellular (diagnostic imaging, metabolism)
• Cell Line, Tumor
• Humans
• Isotope Labeling (methods)
• Lipoproteins, LDL (chemistry, pharmacokinetics)
• Male
• Maleimides (chemistry, pharmacokinetics)
• Metabolic Clearance Rate
• Organ Specificity
• Radionuclide Imaging
• Radiopharmaceuticals (chemical synthesis, pharmacokinetics)
• Rats
• Rats, Wistar
• Tissue Distribution