An efficient one‐step radiosynthesis of [18F]FE‐PE2I, a PET radioligand for imaging of dopamine transporters

Abstract

The aim of this study was to develop a direct fluorination method for the preparation of [18F]‐(E)‐N‐(3‐iodoprop‐2‐enyl)‐2β‐carbofluoroethoxy‐3β‐(4′‐methyl‐phenyl)nortropane ([18F]FE‐PE2I (VI). The synthesis procedure relies on the conventional Kryptofix‐mediated nucleophilic 18F‐substitution of the tosylate group in the precursor, TsOE‐PE2I (V). Out of reaction conditions tested, the highest fluorination efficiency was obtained in dimethyl sulfoxide at 140°C. The reaction mixture was purified by semi‐preparative HPLC, followed‐up by a standard Sep‐Pak SPE procedure. On average, 1.0 GBq of [18F]FE‐PE2I was produced from 5‐min irradiation at 35 μA (dimethyl sulfoxide, 5 min/140°C). Decay‐uncorrected yield of the product after HPLC purification and formulation was in the order of 20%. Specific radioactivity of [18F]FE‐PE2I at 15 min after EOS was 3.3–5.1 Ci/µmol (n = 3); radiochemical purity was >98% (n = 4). This direct nucleophilic fluorination strategy is well suited for the automation of the entire synthesis of [18F]FE‐PE2I in a modern PET synthesizer for human PET application. In addition, the 18F‐incorporation rate into TsOE‐PE2I was evaluated using radio‐thin layer chromatography (TLC) and radio‐HPLC. The suggested HPLC method (ACE 5 C18‐HL column and acetonitrile/0.1 M NH4CO2 (80:20)) was found to be suitable for evaluation of ‘free’ 18F‐fluoride in the reaction mixture; in addition, this method allowed the detection of three radiolabelled by‐products that were not discernable with the TLC approach. Therefore, we conclude that the HPLC approach may serve as a good alternative to traditional radio‐TLC technique as it provides more detailed information about the fluorination process in the reaction kinetics or optimization studies. Copyright © 2012 John Wiley & Sons, Ltd.