title: Fully automated synthesis of 4-[18F]fluorobenzylamine based on borohydride/NiCl2 reduction.
abstract: BACKGROUND
  4-[(18)F]Fluorobenzylamine ([(18)F]FBA) is an important building block for the synthesis of (18)F-labeled compounds. Synthesis of [(18)F]FBA usually involves application of strong reducing agents like LiAlH4 which is challenging to handle in automated synthesis units (ASUs). Therefore, alternative methods for the preparation of [(18)F]FBA compatible with remotely-controlled syntheses in ASUs are needed.
  
  
  METHODS
  (18)F]FBA was prepared in a remotely-controlled synthesis unit (GE TRACERlab™ FX) based on Ni(II)-mediated borohydride exchange resin (BER) reduction of 4-[(18)F]fluorobenzonitrile ([(18)F]FBN). [(18)F]FBA was used for the synthesis of novel thiol-reactive prosthetic group 4-[(18)F]fluorobenzyl)maleimide [(18)F]FBM and Hsp90 inhibitor 17-(4-[(18)F]fluorobenzylamino)-17-demethoxy-geldanamycin [(18)F] GA.
  
  
  RESULTS
  [(18)F]FBA could be prepared in high radiochemical yield greater than 80% (decay-corrected) within 60min. In a typical experiment, 7.4GBq of [(18)F]FBA could be obtained in high radiochemical purity of greater than 95% starting from 10GBq of cyclotron-produced n.c.a. [(18)F]fluoride. [(18)F]FBA was used for the preparation of 4-[(18)F]fluorobenzyl)maleimide as a novel prosthetic group for labeling of thiol groups as demonstrated with tripeptide glutathione. [(18)F]FBA was also used as building block for the syntheses of small molecules as exemplified by the preparation of Hsp90 inhibitor 17-(4-[(18)F]fluorobenzylamino)-17-demethoxy-geldanamycin.
  
  
  CONCLUSIONS
  The described remotely-controlled synthesis of [(18)F]FBA will significantly improve the availability of [(18)F]FBA as an important and versatile building block for the development of novel (18)F-labeled compounds containing a fluorobenzylamine moiety.
authors.affiliation: Department of Oncology, University of Alberta, Edmonton AB, T6G 1Z2, Canada.
authors.forename: Jenilee
authors.initials: J
authors.lastname: Way
authors.forename: Frank
authors.initials: F
authors.lastname: Wuest
mesh_terms: D000478:Alkylation; D001331:Automation; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry*; D001894:Borohydrides / Q000737:chemistry*; D005240:Feasibility Studies; D009532:Nickel / Q000737:chemistry*; D010084:Oxidation-Reduction; D011854:Radiochemistry / Q000379:methods*
chemical_list: D001549:Benzamides; D001894:Borohydrides; C114760:4-fluorobenzylamine; C022838:nickel chloride; D009532:Nickel