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

Introduction: A novel one-pot method for preparing [F-18]fluoromethylcholine ([F-18]FCH) via in situ generation of [F-18]fluoromethyl tosylate ([F-18]FCH2OTs), and subsequent [F-18]fluoromethylation of dimethylaminoethanol (DMAE), has been developed. Methods: [F-18]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 [F-18]FCH2OTs. DMAE was then added and the reaction was heated at 120 degrees C for 10 min to generate [F-18]FCH. After this time, reaction solvent was evaporated, and the crude reaction mixture was purified by solid-phase extraction using C-18-Plus and CM-Light Sep-Pak cartridges to provide [F-18]FCH formulated in USP saline. The formulated product was passed through a 0.22 mu m filter into a sterile dose vial, and submitted for quality control testing. Total synthesis time was 1.25 h from end-of-bombardment. Results: Typical non-decay-corrected yields of [F-18]FCH prepared using this method were 91 mCi (7% non-decay corrected based upon similar to 13 Ci [F-18]fluoride), and doses passed all other quality control (QC) tests. Conclusion: A one-pot liquid-phase synthesis of [F-18]FCH has been developed. Doses contain extremely low levels of residual DMAE (31.6 mu g/10 mL dose or similar to 3 ppm) and passed all other requisite QC testing, confirming their suitability for use in clinical imaging studies. (c) 2013 Elsevier Ltd. All rights reserved.