Radio fluorination and positron emission tomography (PET) as a new approach to study the in vivo distribution and elimination of the advanced glycation endproducts N epsilon-carboxymethyllysine (CML) and N epsilon-carboxyethyllysine (CEL).
After synthesis of fluorine-18 labelled analogues by [18F]fluorobenzoylation at the alpha-amino group, biodistribution and elimination of individual advanced glycation endproducts, namely N epsilon-carboxymethyllysine and N epsilon-carboxyethyllysine, were studied in comparison to lysine in rats after intravenous injection using positron emission tomography (PET). The [18F]radiofluorinated amino acids were fast distributed via the blood, followed by a rapid excretion through the kidneys. Elimination kinetics were similar for both AGEs and lysine. For CML and CEL, but not for lysine, a temporary liver accumulation could be observed, which was not connected with any metabolisation or enterohepatic circulation. No further accumulation in any tissues was observable, indicating that increased tissue levels of CML or CEL, which have been described for certain disorders, are exclusively derived from endogenous origin and should not depend on a dietary intake. However, under uremic conditions, an impaired kidney function might result in a significant increase of the AGE-load of blood and tissues. PET based on 18F-labelled AGEs proved to be a promising tool to elucidate the physiological fate of post-translationally modified amino acids and to clarify the role of AGEs as possible "glycotoxins".
Bergmann
R
R
Research Centre Rossendorf, Institute of Bioinorganic and Radiopharmaceutical Chemistry, Rossendorf.
Helling
R
R
Heichert
C
C
Scheunemann
M
M
Mäding
P
P
Wittrisch
H
H
Johannsen
B
B
Henle
T
T
D000818:Animals; D005462:Fluorine Radioisotopes; D017127:Glycation End Products, Advanced / Q000493:pharmacokinetics* / Q000502:physiology; D006207:Half-Life; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*
D005462:Fluorine Radioisotopes; D017127:Glycation End Products, Advanced