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Background  N ε -carboxymethyl-lysine (CML) is a major advanced glycation end-product (AGEs) widely found in foods. The aim of our study was to evaluate how exogenous CML-peptide is dynamically absorbed from the gastrointestinal tract and eliminated by renal tubular secretion using microPET imaging.    Methods  The present study consisted of three investigations. In study I, we synthesized the imaging tracer  18 F-CML by reacting N-succinimidyl 4- 18 F-fluorobenzoate ( 18 F-SFB) with CML. In study II, the biological activity of  18 F-CML was evaluated in RAW264.7 cells and HepG2 cells. In study III, the biodistribution and elimination of AGEs in ICR mice were studied in vivo following tail vein injection and intragastric administration of  18 F-CML.    Result  The formation of  18 F-CML was confirmed by comparing its retention time with the corresponding reference compound  19 F-CML. The radiochemical purity (RCP) of  18 F-CML was >95%, and it showed a stable character in vitro and in vivo. Uptake of  18 F-CML by RAW264.7 cells and HepG2 cells could be inhibited by unmodified CML.  18 F-CML was quickly distributed via the blood, and it was rapidly excreted through the kidneys 20 min after tail vein injection. However,  18 F-CML was only slightly absorbed following intragastric administration. After administration of  18 F-CML via a stomach tube, the radioactivity was completely localized in the stomach for the first 15 min. At 150 min post intragastric administration, intense accumulation of radioactivity in the intestines was still observed.    Conclusions  PET technology is a powerful tool for the in vivo analysis of the gastrointestinal absorption of orally administered drugs.  18 F-CML is hardly absorbed by the gastrointestinal tract. It is rapidly distributed and eliminated from blood following intravenous administration. Thus, it may not be harmful to healthy bodies. Our study showed the feasibility of noninvasively imaging  18 F-labeled AGEs and was the first to describe CML-peptide gastrointestinal absorption by means of PET.

Biodistribution and Elimination Study of Fluorine-18 Labeled Nε-Carboxymethyl-Lysine following Intragastric and Intravenous Administration