Abstract
BackgroundNε-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.MethodsThe present study consisted of three investigations. In study I, we synthesized the imaging tracer 18F-CML by reacting N-succinimidyl 4-18F-fluorobenzoate (18F-SFB) with CML. In study II, the biological activity of 18F-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 18F-CML.ResultThe formation of 18F-CML was confirmed by comparing its retention time with the corresponding reference compound 19F-CML. The radiochemical purity (RCP) of 18F-CML was >95%, and it showed a stable character in vitro and in vivo. Uptake of 18F-CML by RAW264.7 cells and HepG2 cells could be inhibited by unmodified CML. 18F-CML was quickly distributed via the blood, and it was rapidly excreted through the kidneys 20 min after tail vein injection. However, 18F-CML was only slightly absorbed following intragastric administration. After administration of 18F-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.ConclusionsPET technology is a powerful tool for the in vivo analysis of the gastrointestinal absorption of orally administered drugs. 18F-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 18F-labeled AGEs and was the first to describe CML-peptide gastrointestinal absorption by means of PET.
Highlights
Advanced glycation end-products (AGEs) are a heterogeneous group of compounds that are formed when reducing sugar reacts in a non-enzymatically with amino acids in proteins and other macromolecules [1]
Positron emission tomography (PET) technology is a powerful tool for the in vivo analysis of the gastrointestinal absorption of orally administered drugs. 18F-CML is hardly absorbed by the gastrointestinal tract
Our study showed the feasibility of noninvasively imaging 18F-labeled AGEs and was the first to describe CML-peptide gastrointestinal absorption by means of PET
Summary
Advanced glycation end-products (AGEs) are a heterogeneous group of compounds that are formed when reducing sugar reacts in a non-enzymatically with amino acids in proteins and other macromolecules [1]. Other studies have shown that exogenous AGEs are not absorbed by the gastrointestinal tract and are not toxic to human health [9,10,11]. These findings indicate that the different biodistributions of AGEs may be related to the different functional effects of AGEs [10,12]. It is still not clear whether elevated exposure to AGEs contributes to AGE deposition in tissues. 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
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