Synthesis of [18F]FETO, a novel potential 11-β hydroxylase inhibitor

Recent publications reported high uptake of the carbon-(11) labelled 11beta-hydroxylase inhibitors (R)-[O-methyl-C-11]metomidate ([C-11]MTO) and (R)[O-ethyl-C-11]etomidate ([C-11]ETO) in adrenocortical incidentalomas with excellent selectivity for positron emission tomography (PET). In our studies [F-18]FETO, (the [F-18]fluoroethyl ester of etomidate, (R)-1-(I-phenylethyl)-1H-imidazole-5-carboxylic acid, 2'-[F-18]fluoroethyl ester), an analogue of [C-11]MTO and [C-11]ETO was chosen due to the suspected similarity of the pharmacokinetic and pharmacodynamic properties, and was prepared in the following two step procedure: First, [F-18]fluoride was reacted with 2-bromoethyl triflate using the kryptofix/acetonitrile method to yield 2-bromo-[F-18]fluoroethane ([F-18]BFE). in the second step, [F-18]BFE was reacted with the tetrabutylammonium salt of (R)-1-(I-phenylethyl)-1H-imidazole-5-carboxylic acid to yield [F-18]FETO, a novel inhibitor of the 11beta-hydroxylase. The proposed synthesis of [F-18]FETO allows the production of sufficient amounts of this new PET-tracer to serve 1-2 patients with an overall synthesis time of less than 80 min. Copyright (C) 2003 John Wiley Sons, Ltd.