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]fluorobenzoylatio n 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 af ter intravenous injection using positron emission tomography (PET). The [F-18]radiofluorinatrd amino acids were fast distributed via the blood, followed by a rapid excretion through the kidneys. Elimination kinetics we re similar for both AGEs and lysine. For CML and GEL, but not for lysine, a temporary liver accumulation could be observed. which was not connected wi th any metabolisation or enterohepatic circulation. No further accumulation in any tissues was observable, indicating that increased tissue levels of CML or GEL, which have been described for certain disorders, are exclusivel y derived from endogenous origin and should nor depend on a dietary intake. However, under uremic conditions, an impaired kidney function might result in a significant increase of the AGE-load of blued and tissues. PET based on F-18-labelled AGEs proved to be a promising tool to elucidate the physio logical fate of post-translationally modified amino acids and to clarify th e role of AGEs as possible "glycotoxins".