A simplified GMP-compliant cassette synthesis for ruthenium-mediated 18F-deoxyfluorination of [18F]FPATPP from a phenolic precursor

• This study shows a straightforward Ru-mediated deoxyradiofluorination of phenols without a separate complexation of the precursor. • The synthesis was automated in a GMP compliant cassette device. • [ 18 F]FPATPP was synthesized with good radiochemical yield and high molar activity. • The amount of residual ruthenium in this method is well below the daily limitations. Ruthenium-mediated 18 F-deoxyfluorination of phenols is a fairly new, but highly underutilized, labeling method option of tracers for positron emission tomography (PET). Most of the published methods are directed toward peptide syntheses and include extensive preparation steps. This study aimed to simplify ruthenium-mediated 18 F-deoxyfluorination of [ 18 F]FPATPP by using the TRASIS AllinOne synthesis platform. This protocol takes minimal preparation time (1 h) and applies a straightforward synthesis that can be used to produce tracers from their electron-rich phenolic precursors bearing protic functional groups such as alcohols and amines. The new simplified cassette method afforded a novel cannabinoid receptor 1 specific tracer [ 18 F]FPATPP with a radiochemical yield of 34 ± 2 %, radiochemical purity of ≥ 97 %, and a molar activity of 620 ± 75 GBq/µmol. The total synthesis time was 55 min. In addition, we developed an attachable accessory compatible with TRASIS AllinOne to enable needle movement to enhance the synthesis yield. Our results broaden the possibilities of a cassette based synthesis development for 18 F-labeled molecules and bridge the gap between research and GMP compatible synthesis methods.