title: Biodistribution and catabolism of 18F-labeled N-epsilon-fructoselysine as a model of Amadori products.
abstract: Amadori products are formed in the early stage of the so-called Maillard reaction between reducing sugars and amino acids or proteins. Such nonenzymatic glycosylation may occur during the heating or storage of foods, but also under physiological conditions. N-epsilon-fructoselysine is formed via this reaction between the epsilon-amino group of peptide-bound lysine and glucose. Despite the fact that, in certain heated foods, up to 50% of lysyl moieties may be modified to such lysine derivatives, up to now, very little is known about the metabolic fate of alimentary administered Amadori compounds. In the present study, N-succinimidyl-4-[18F]fluorobenzoate was used to modify N-epsilon-fructoselysine at the alpha-amino group of the lysyl moiety. The in vitro stability of the resulting 4-[18F]fluorobenzoylated derivative was tested in different tissue homogenates. Furthermore, the 4-[18F]fluorobenzoylated N-epsilon-fructoselysine was used in positron emission tomography studies, as well as in studies concerning biodistribution and catabolism. The results show that the 4-[18F]fluorobenzoylated N-epsilon-fructoselysine is phosphorylated in vitro, as well as in vivo. This phosphorylation is caused by fructosamine 3-kinases and occurs in vivo, particularly in the kidneys. Despite the action of these enzymes, it was shown that a large part of the intravenously applied radiolabeled N-epsilon-fructoselysine was excreted nearly unchanged in the urine. Therefore, it was concluded that the predominant part of peptide-bound lysine that was fructosylated during food processing is not available for nutrition.
authors.affiliation: Institute of Radiopharmacy, Research Center Rossendorf, P.O. Box 51 01 19, D-01314 Dresden, Germany. ch.hultsch@fz-rossendorf.de
authors.forename: Christina
authors.initials: C
authors.lastname: Hultsch
authors.forename: Michael
authors.initials: M
authors.lastname: Hellwig
authors.forename: Beate
authors.initials: B
authors.lastname: Pawelke
authors.forename: Ralf
authors.initials: R
authors.lastname: Bergmann
authors.forename: Katrin
authors.initials: K
authors.lastname: Rode
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
authors.forename: René
authors.initials: R
authors.lastname: Krause
authors.forename: Thomas
authors.initials: T
authors.lastname: Henle
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D008239:Lysine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015416:Maillard Reaction; D008297:Male; D008657:Metabolic Clearance Rate; D008660:Metabolism; D009928:Organ Specificity; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C033186:fructosyl-lysine; D008239:Lysine