Biodistribution and catabolism of 18F-labeled N-epsilon-fructoselysine as a model of Amadori products

Nucl Med Biol. 2006 Oct;33(7):865-73. doi: 10.1016/j.nucmedbio.2006.07.007.

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.

MeSH terms

  • Animals
  • Fluorine Radioisotopes / pharmacokinetics
  • Lysine / analogs & derivatives*
  • Lysine / pharmacokinetics
  • Maillard Reaction*
  • Male
  • Metabolic Clearance Rate
  • Metabolism
  • Organ Specificity
  • Positron-Emission Tomography
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Wistar
  • Tissue Distribution

Substances

  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • fructosyl-lysine
  • Lysine