Synthesis of [18F]3-[1-(3-fluoropropyl)-(S)pyrrohdin-2-ylmethoxylpyridine ([18F]NicFP):: a potential α4β2 nicotinic acetylcholine receptor radioligand for PET

Nicotinic acetylcholine receptors are widely distributed throughout the human brain and are believed to play a role in several neurological and psychiatric disorders. In order to identify an effective PET radioligand for in vivo assessment of the alpha4beta2 subtype of nicotinic receptor, we synthesized [F-18]3-[1-(3-fluoropropyl)-(S)-pyrrolidin-2-ylmethoxy]pyridine (NicFP). The in vitro K-D of NicFP was determined to be 1.1 nM, and the log P value obtained by HPLC analysis of the unlabelled standard was found to be 2.2. The radiosynthesis of [F-18]NicFP was carried out by a nucleophilic substitution reaction of anhydrous [F-18]fluoride and the corresponding mesylate precursor. After purification by HPLC, the radiochemical yield was determined to be 11.3 +/- 2.1% and the specific activity was 0.47 +/- 0.18 Ci/mumol (EOS, n = 3). The time of synthesis and purification was 99 +/- 2 min. The final product was prepared as a sterile saline solution suitable for in vivo use. Copyright C) 2003 John Wiley Sons, Ltd.