[18F]FETO: Metabolic considerations

Author(s)
Dagmar E. Ettlinger, Wolfgang Wadsak, Leonhard-Key Mien, Michael Machek, Leila Wabnegger, Gundula Rendl, Georgios Karanikas, Helmut Viernstein, Kurt Kletter, Robert Dudczak, Markus Mitterhauser
Abstract

Purpose: 11ß-Hydroxylase is a key enzyme in the biosynthesis of adrenocortical steroid hormones and is a suitable target for the imaging of the adrenal cortex. [11C]Metomidate (MTO), [11C]etomidate (ETO) and desethyl-[18F]fluoroethyl-etomidate (FETO) are potent inhibitors of this enzyme and are used for PET imaging of adrenocortical pathologies. The aims of this study were (1) to evaluate and compare the metabolic stability of MTO, ETO and FETO against esterases and (2) to investigate the metabolic pattern of FETO in vivo. Methods: In vitro assays were performed using different concentrations of MTO, ETO and FETO with constant concentrations of carboxylesterase. Human in vivo studies were performed with human blood samples drawn from the cubital vein. After sample clean-up, the serum was analysed by HPLC methods. Results: In vitro assays showed Michaelis-Menten constants of 115.1 œmol for FETO, 162.0 œmol for MTO and 168.6 œmol for ETO. Limiting velocities were 1.54 œmol/min (FETO), 1.47 œmol/min (MTO) and 1.35 œmol/min (ETO). This implies insignificantly decreased esterase stability of FETO compared with MTO and ETO. In vivo investigations showed a rapid metabolisation of FETO within the first 10 min (2 min: 91.41%‘6.44%, n=6; 10 min: 23.78%‘5.54%, n=4) followed by a smooth decrease in FETO from 20 to 90 min (20 min: 11.23%‘3.79% n=4; 90 min: 3.68%‘3.65%, n=4). Recovery rate was 61.43%‘3.19% (n). Conclusion: In vitro experiments demonstrated that FETO stability against esterases is comparable to that of ETO and MTO. The metabolic profile showed that FETO kinetics in humans are fast. Œ Springer-Verlag 2006.

Organisation(s)
Department of Inorganic Chemistry, Department of Sport and Human Movement Science
External organisation(s)
Medizinische Universität Wien
Journal
European Journal of Nuclear Medicine and Molecular Imaging
Volume
33
Pages
928-931
No. of pages
4
ISSN
1619-7070
Publication date
2006
Peer reviewed
Yes
Austrian Fields of Science 2012
3012 Pharmacy, Pharmacology, Toxicology
Portal url
https://ucrisportal.univie.ac.at/en/publications/fb25f2d0-7263-4b25-85ad-7178a299973b