title: A fully-automated one-pot synthesis of [18F]fluoromethylcholine with reduced dimethylaminoethanol contamination via [18F]fluoromethyl tosylate.
abstract: BACKGROUND
  A novel one-pot method for preparing [(18)F]fluoromethylcholine ([(18)F]FCH) via in situ generation of [(18)F]fluoromethyl tosylate ([(18)F]FCH2OTs), and subsequent [(18)F]fluoromethylation of dimethylaminoethanol (DMAE), has been developed.
  
  
  METHODS
  [(18)F]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 [(18)F]FCH2OTs. DMAE was then added and the reaction was heated at 120 °C for 10 min to generate [(18)F]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 [(18)F]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.
  
  
  RESULTS
  Typical non-decay-corrected yields of [(18)F]FCH prepared using this method were 91 mCi (7% non-decay corrected based upon ~1.3 Ci [(18)F]fluoride), and doses passed all other quality control (QC) tests.
  
  
  CONCLUSIONS
  A one-pot liquid-phase synthesis of [(18)F]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.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Rodnick
authors.forename: Allen F
authors.initials: AF
authors.lastname: Brooks
authors.forename: Brian G
authors.initials: BG
authors.lastname: Hockley
authors.forename: Bradford D
authors.initials: BD
authors.lastname: Henderson
authors.forename: Peter J H
authors.initials: PJ
authors.lastname: Scott
mesh_terms: D002794:Choline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification; D003642:Deanol / Q000737:chemistry* / Q000302:isolation & purification*; D004340:Drug Contamination / Q000517:prevention & control*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D007553:Isotope Labeling / Q000295:instrumentation* / Q000379:methods; D012371:Robotics / Q000295:instrumentation* / Q000379:methods
chemical_list: C516370:fluoromethylcholine; D003642:Deanol; D002794:Choline