A Practical One-Pot Synthesis of Positron Emission Tomography (PET) Tracers via Nickel-Mediated Radiofluorination

Abstract

Recently a novel method for the preparation of F-18-labeled arenes via oxidative [F-18] fluorination of easily accessible and sufficiently stable nickel complexes with [F-18] fluoride under exceptionally mild reaction conditions was published. The suitability of this procedure for the routine preparation of clinically relevant positron emission tomography (PET) tracers, 6[-F-18]fluorodopamine (6-[F-18]FDA), 6-[F-18]fluoro-l-DOPA (6-[F-18]FDOPA) and 6-[F-18]fluoro-m-tyrosine (6-[F-18]FMT), was evaluated. The originally published base-free method was inoperative. However, a "low base" protocol afforded protected radiolabeled intermediates in radiochemical conversions (RCCs) of 5-18 %. The subsequent deprotection step proceeded almost quantitatively (> 95 %). The simple one-pot two-step procedure allowed the preparation of clinical doses of 6-[F-18]FDA and 6-[F-18]FDOPA within 50 min (12 and 7% radiochemical yield, respectively). In an unilateral rat model of Parkinson's disease, 6-[F-18]FDOPA with high specific activity (175 GBq mu mol(-1)) prepared using the described nickel-mediated radiofluorination was compared to 6-[F-18] FDOPA with low specific activity (30 MBq mu mol(-1)) produced via conventional electrophilic radiofluorination. Unexpectedly both tracer variants displayed very similar in vivo properties with respect to signal-to-noise ratio and brain distribution, and consequently, the quality of the obtained PET images was almost identical.