Biodistribution and catabolism of 18F-labeled N-epsilon-fructoselysine as a model of Amadori products.
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.
Hultsch
Christina
C
Institute of Radiopharmacy, Research Center Rossendorf, P.O. Box 51 01 19, D-01314 Dresden, Germany. ch.hultsch@fz-rossendorf.de
Hellwig
Michael
M
Pawelke
Beate
B
Bergmann
Ralf
R
Rode
Katrin
K
Pietzsch
Jens
J
Krause
René
R
Henle
Thomas
T
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
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C033186:fructosyl-lysine; D008239:Lysine