title: Electrophilic addition of chlorine monofluoride for PET tracers.
abstract: OBJECTIVE
  We have studied the utility of [(18)F]ClF electrophilic addition to the carbon-carbon double bond of analogues of a model positron emission tomography (PET) tracer, [(18)F]EF5. The consequence of simultaneous chlorine/fluorine addition on lipophilicity and biological activity of the molecule is evaluated.
  
  
  METHODS
  Post-target produced [(18)F]F2 was reacted with Cl2 to produce [(18)F]ClF, which was used in electrophilic addition.
  
  
  RESULTS
  [(18)F]ClF was produced and used to label chlorinated analogues of [(18)F]EF5. The chlorinated analogues, [(18)F]EF4Cla and [(18)F]EF4Clb, were synthesized simultaneously. The in vivo uptake of the analogues compared well with [(18)F]EF5 uptake in tumor-bearing mice.
  
  
  CONCLUSIONS
  [(18)F]ClF is a suitable labeling reagent for electrophilic addition to double bonds of PET tracers. The results show that the modification of the pentafluoro group of [(18)F]EF5 by monofluorine-for-chlorine exchange affected the lipophilicity, but the hypoxia avidity of these molecules was not apparently altered.
authors.affiliation: Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kirjavainen
authors.forename: Sarita
authors.initials: S
authors.lastname: Forsback
authors.forename: Tove J
authors.initials: TJ
authors.lastname: Grönroos
authors.forename: Laura
authors.initials: L
authors.lastname: Haavisto
authors.forename: Merja
authors.initials: M
authors.lastname: Haaparanta
authors.forename: Olof
authors.initials: O
authors.lastname: Solin
mesh_terms: D000818:Animals; D002712:Chlorides / Q000737:chemistry* / Q000493:pharmacokinetics; D017341:Etanidazole / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D005459:Fluorides / Q000737:chemistry* / Q000493:pharmacokinetics; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D005466:Fluorocarbons
chemical_list: D002712:Chlorides; D017341:Etanidazole; D005459:Fluorides; D006845:Hydrocarbons, Fluorinated; D019275:Radiopharmaceuticals; C096011:2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide; D005466:Fluorocarbons