Radiosynthesis of F-18 PBR111, a selective radioligand for imaging the translocator protein (18 kDa) with PET

Abstract

PBR111 (2-(6-chloro-2-(4-(3-fluoro-propoxy)phenyl)imidazo[1,2-a]pyridin-3-yl)-N, N-diethylacetamide) is a novel, reported, high-affinity and selective ligand for the translocator protein (18 kDa). PBR111 has been labelled with fluorine-18 (half-life: 109.8 min) using our Zymate-XP robotic system. The process involves (A) a simple one-step to syloxy-for-fluorine nucleophilic aliphatic substitution (performed at 165 degrees C for 5 min in DMSO using K[18F]F-Kryptofix 222 and 6.8-7.6 μ mol of the corresponding tosylate as precursor for labelling) followed by (B) C-18 PrepSep cartridge pre-purification and(C) semi-preparative HPLC purification on a Waters Symmetry C-18. Up to 4.8 GBq (130 mCi) of [18F]PBR111 could be obtained with specific radioactivities ranging from 74 to 148 GBq/μ mol (2-4 Ci/μ mol) in 75-80 min (HPLC purification and SepPak-based formulation included), starting from a 37.0 GBq (1.0 Ci) [18F]fluoride batch. Overall non-decay-corrected isolated yields were 8-13% (13-21% decay-corrected). © 2008 John Wiley & Sons, Ltd.