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".

Determination of titanocene, a new drug with anticancer potential, and its metabolism in solution by capillary electrophoresis.

Titanocene dichloride is one of the most promising cancerostatica of the future: nevertheless, its high activity against several tumor cells was discovered 20 years ago. Detailed knowledge of the mechanism of hydrolysis of titanocene dichloride and its stability in the infusion liquid is a prerequisite for clinical tests and for a successful application for permission as medication. Capillary electrophoresis (CE) was used to observe the hydrolysis behavior of titanocene dichloride in aqueous solutions. The hydrolysis products were separated in a 20 mM phosphate buffer, pH 6, and in a 20 mM malic acid buffer, pH 3. Up to five hydrolysis products were obtained. A significant influence of the sample preparation (pH, isoionic additives) on the hydrolysis rate was observed. The hydrolysis products were characterized by the UV scan and the element-selective particle-induced X-ray emission (PIXE) detection technique. The results obtained correspond with the hydrolysis mechanism described in the literature. The determination of free titanocene dichloride in human plasma failed due to the high affinity of the plasma proteins for this compound.