Radiosynthesis of the norepinephrine transporter tracer [18F]NS12137 via copper-mediated 18F-labelling

Abstract

[18F]NS12137 (exo-3-[(6-[18F]fluoro-2-pyridyl)oxy]8-azabicyclo[3.2.1]octane) is a highly selective norepinephrine transporter (NET) tracer. NETs are responsible for the reuptake of norepinephrine and dopamine and are linked to several neurodegenerative and neuropsychiatric disorders. The aim of this study was to develop a copper-mediated 18F-fluorination method for the production of [18F]NS12137 with straightforward synthesis conditions and high radiochemical yield and molar activity. [18F]NS12137 was produced in two steps. Radiofluorination of [18F]NS12137 was performed via a copper-mediated pathway starting with a stannane precursor and using [18F]F− as the source of the fluorine-18 isotope. Deprotection was performed via acid hydrolysis. The radiofluorination reaction was nearly quantitative as was the deprotection based on HPLC analysis. The radiochemical yield of the synthesis was 15.1 ± 0.5%. Molar activity of [18F]NS12137 was up to 300 GBq/μmol. The synthesis procedure is straightforward and can easily be automated and adapted for clinical production.