Background: 2-[18F]Fluoroethyltosylate ([18F]FEtOTs) is a well-known 18F-fluoroalkylating agent widely used to synthesize radiotracers for positron emission tomography. The widespread use of [18F]FEtOTs is due in part to its low volatility when compared to other halide and sulfonate building blocks. In this work, the radioactive volatile side-products formed during the synthesis of [18F]FEtOTs were identified and characterized for the first time, and an optimization of the reaction conditions to minimize their formation was proposed.
Results: In order to characterize the volatiles produced during [18F]FEtOTs synthesis, the reaction mixtures of both cold FEtOTs and [18F]FEtOTs were co-injected onto the HPLC system. The radioactive peaks corresponding to the volatile compounds were collected, analyzed through headspace gas chromatography mass spectrometry sampler (HS-GC-MS) and identified as vinyl fluoride ([19F]VF) and 2-fluoroethanol ([19F]FEOH). By using a rotatable central composite design with a two-level full factorial core of two factors (22), it was determined that temperature and time are independent variables which affect the generation of [18F]VF and [18F]FEOH during the radiosynthesis of [18F]FEtOTs. In addition, in order to reduce the formation of the volatiles ([18F]VF and [18F]FEOH) and increase the yield of [18F]FEtOTs, it was demonstrated that the molar ratio of base to precursor must also be considered.
Conclusion: [18F]VF and [18F]FEOH are volatile side-products formed during the radiosynthesis of [18F]FEtOTs, whose yields depend on the reaction time, temperature, and the molar ratio of base to precursor. Therefore, special care should be taken during the radiosynthesis and subsequent reactions using [18F]FEOTs in order to avoid environmental contamination and to improve the yield of the desired products.
Keywords: 2-[18F]Fluoroethyl tosylate; 2-[18F]fluoroethanol; PET tracers; Radiation safety; Radioactive gas; [18F]vinyl fluoride.
© 2022. The Author(s).