title: Efficient preparation of [11C]CH3Br for the labeling of [11C]CH3-containing tracers in positron emission tomography clinical practice.
abstract: OBJECTIVE
  [C]methyl iodide ([C]CH3I) is the most extensively used methylation agent for the preparation of a majority of C-labeled positron emission tomography (PET) radiotracers, which is commonly produced by the wet method and the gas-phase method. On account of the complexity of the gas-phase method, a simple automated synthesis of [C]methyl bromide ([C]CH3Br) as an analog of [C]CH3I is derived by the wet method in this study. Radiosynthesis of L-[S-methyl-C]methionine (MET), L-[S-methyl-C]cysteine (MCYS), [N-methyl-C]choline (CH), [C]methyl triflate ([C]CH3OSO2CF3), and [C]-2-β-carbomethoxy-3-β-(4-fluorophenyl)-tropane (CFT) by methylation reaction with [C]CH3Br, and PET imaging of patients are also described.
  
  
  METHODS
  The preparation of [C]CH3Br by a one-pot wet method involved the following steps: reduction of [C]carbon dioxide with lithium aluminium hydride (LiAlH4) solution, treatment with hydrobromic acid, and distillation of [C]CH3Br under continuous nitrogen flow. [C]methylation of L-homocysteine thiolactone hydrochloride, L-cysteine, 2-dimethylaminoethanol, silver triflate, and nor-β-CFT as precursors with [C]CH3Br and purification with Sep-Pak cartridges gave MET, MCYS, CH, [C]CH3OSO2CF3, and CFT, respectively. In addition, PET imaging of brain cancer and Parkinson's disease was carried out.
  
  
  RESULTS
  The uncorrected radiochemical yield of [C]CH3Br was (37.8±2.5%) based on [C]carbon dioxide within a total synthesis time of 10 min and the radiochemical purity of [C]CH3Br was greater than 95%. The uncorrected yields of MET, MCYS, CH, [C]CH3OSO2CF3, and CFT were 70.1±0.5%, 70.2±2.3%, 60.3±1.8%, 95.1±2.2%, and 60.1±1.5% (from [C]CH3OSO2CF3) within a total synthesis time of 2, 2, 5, 1, and 8 min, respectively. The radiochemical purity of MET, MCYS, CH, [C]CH3OSO2CF3, and CFT was more than 95%. Good PET images in the patients are obtained.
  
  
  CONCLUSIONS
  Automated synthesis of [C]CH3Br can be done by the wet method on the commercial [C]CH3I synthesizer. [C]CH3Br can be used for a [C]methylation reaction to produce C-labeled tracers for clinical PET imaging.
authors.affiliation: PET-CT Center, Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. gtang0224@yahoo.com.cn
authors.forename: Ganghua
authors.initials: G
authors.lastname: Tang
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Tang
authors.forename: Huaifu
authors.initials: H
authors.lastname: Deng
authors.forename: Hongliang
authors.initials: H
authors.lastname: Wang
authors.forename: Fuhua
authors.initials: F
authors.lastname: Wen
authors.forename: Chang
authors.initials: C
authors.lastname: Yi
authors.forename: Kening
authors.initials: K
authors.lastname: Wu
mesh_terms: D000577:Amides / Q000737:chemistry; D002250:Carbon Radioisotopes / Q000737:chemistry; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000138:chemical synthesis* / Q000737:chemistry; D007553:Isotope Labeling; D008745:Methylation; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers; D011854:Radiochemistry / Q000379:methods*; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000577:Amides; D002250:Carbon Radioisotopes; D006842:Hydrocarbons, Brominated; D011849:Radioactive Tracers; D013438:Sulfhydryl Compounds; C005218:methyl bromide