title: Facile and rapid one-step radiosynthesis of [(18)F]BAY94-9172 with a new precursor.
abstract: BACKGROUND
  [(18)F]BAY94-9172 (Florbetaben) (Compound 8) is a positron emission tomography (PET) tracer that is currently in Phase III study for in vivo mapping of fibrillar amyloid β as a pathological hallmark for Alzheimer's disease. This work reports new methods for the synthesis of [(19)F]BAY94-9172 and its two different precursors and radiosynthesis of [(18)F]BAY94-9172 with the two precursors by purification using Sep-Pak cartridge.
  
  
  METHODS
  The reference standard [(19)F]BAY94-9172 and the new precursor (Compound 9) were obtained from the reactions of (E)-4-methylamino-4'-hydroxystilbene (Compound 1) with methanesulfonic acid 2-[2-(2-fluoro-ethoxy)-ethoxy]-ethyl ester (Compound 11) and methanesulfonic acid 2-[2-(2-methanesulfonyloxy-ethoxy)-ethoxy]-ethyl ester (Compound 13), respectively. The reported precursor (Compound 6) is an N-BOC-protected mesylate compound, which was obtained from Compound 9. The one-step radiosynthesis of [(18)F]BAY94-9172 was carried out in the modified PET-MF-2V-IT-1 synthesizer by [(18)F]fluorination of the new precursor (Compound 9) and purification with plus C18 Sep-Pak cartridges and was compared with two-step one-pot radiosynthesis using the reported precursor (Compound 6) and Sep-Pak cartridge purification.
  
  
  RESULTS
  For one-step radiosynthesis, the uncorrected radiochemical yield of [(18)F]BAY94-9172 was 23 ± 3% (n = 5, based on [(18)F]fluoride) within 30 min and the radiochemical purity was greater than 95%. For two-step one-pot radiosynthesis, the uncorrected radiochemical yield of [(18)F]BAY94-9172 was 17 ± 2% in 45 min (n = 4, based on [(18)F]fluoride) with the radiochemical purity being above 95% after the Sep-Pak cartridge purification.
  
  
  CONCLUSIONS
  [(19)F]BAY94-9172 and the two precursors were synthesized by a short synthetic route. Compared with HPLC purification, the use of Sep-Pak purification of [(18)F]BAY94-9172 reduced the total radiosynthesis time. The one-step radiosynthesis of [(18)F]BAY94-9172 is convenient and can easily be applied to the commercial PET tracer synthesizer for automated synthesis.
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Wang
authors.forename: Huixian
authors.initials: H
authors.lastname: Shi
authors.forename: Haiyan
authors.initials: H
authors.lastname: Yu
authors.forename: Shende
authors.initials: S
authors.lastname: Jiang
authors.forename: Ganghua
authors.initials: G
authors.lastname: Tang
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry* / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D007700:Kinetics; D008698:Mesylates / Q000737:chemistry; D011854:Radiochemistry; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D000814:Aniline Compounds; D005462:Fluorine Radioisotopes; D008698:Mesylates; D013267:Stilbenes; C527756:4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene