A fully-automated one-pot synthesis of [18F]fluoromethylcholine with reduced dimethylaminoethanol contamination via [18F]fluoromethyl tosylate

•A novel fully automated synthesis of [18F]fluoromethylcholine has been developed•Typical non-decay-corrected yields were 91 mCi (7% non-decay corrected, n=3)•QC testing confirmed suitability for clinical use (RCP >99%; SA 16,147 Ci/mmol)•Doses contain amongst the lowest residual DMAE ever reported

IntroductionA novel one-pot method for preparing [18F]fluoromethylcholine ([18F]FCH) via in situ generation of [18F]fluoromethyl tosylate ([18F]FCH2OTs), and subsequent [18F]fluoromethylation of dimethylaminoethanol (DMAE), has been developed.Methods[18F]FCH was prepared using a GE TRACERlab FXFN, although the method should be readily adaptable to any other fluorine-18 synthesis module. Initially ditosylmethane was fluorinated to generate [18F]FCH2OTs. DMAE was then added and the reaction was heated at 120 °C for 10 min to generate [18F]FCH. After this time, reaction solvent was evaporated, and the crude reaction mixture was purified by solid-phase extraction using C18-Plus and CM-Light Sep-Pak cartridges to provide [18F]FCH formulated in USP saline. The formulated product was passed through a 0.22 µm filter into a sterile dose vial, and submitted for quality control testing. Total synthesis time was 1.25 h from end-of-bombardment.ResultsTypical non-decay-corrected yields of [18F]FCH prepared using this method were 91 mCi (7% non-decay corrected based upon ∼1.3 Ci [18F]fluoride), and doses passed all other quality control (QC) tests.ConclusionA one-pot liquid-phase synthesis of [18F]FCH has been developed. Doses contain extremely low levels of residual DMAE (31.6 µg/10 mL dose or ∼3 ppm) and passed all other requisite QC testing, confirming their suitability for use in clinical imaging studies.

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