title: Tracer level electrophilic synthesis and pharmacokinetics of the hypoxia tracer [(18)F]EF5.
abstract: OBJECTIVE
  2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide labeled with [(18)F]-fluorine ([(18)F]EF5), a promising tracer for tumor hypoxia, has previously been synthesized in low yields and low specific radioactivity. In pharmacokinetic evaluations, in the presence of non-radioactive EF5, a uniform and low background uptake and high in vivo stability of [(18)F]EF5 have been demonstrated. Our purpose was to increase the specific radioactivity of [(18)F]EF5 to enable to study the pharmacokinetics at trace level.
  
  
  METHODS
  [(18)F]EF5 was synthesized using high specific radioactivity electrophilic [(18)F]F(2) as labelling reagent. Biodistribution of [(18)F]EF5 was determined in a prostate tumor mouse model, and formation of radiolabelled metabolites was studied in mouse, rat and human plasma.
  
  
  RESULTS
  On average, 595 ± 153 MBq of [(18)F]EF5 was produced. Specific radioactivity was 6.6 ± 1.9 GBq/μmol and the radiochemical purity exceeded 99.0%. [(18)F]EF5 was distributed uniformly in tissues, with highest uptake in liver, kidney, and intestine. Several radiolabelled metabolites were detected in mouse plasma and tissues, whereas low amounts of metabolites were detected in human and rat plasma.
  
  
  CONCLUSIONS
  [(18)F]EF5 was synthesized by electrophilic labelling with high quality and high yields. Pharmacokinetics of [(18)F]EF5 was determined at trace level in several species. Our results suggest that the trace-level approach does not affect the biodistribution of [(18)F]EF5. Extensive metabolism was seen in mouse.
authors: Turku PET Centre, Radiopharmaceutical Chemistry Laboratory, University of Turku, Turku, Finland. olesko@utu.fi
authors: Olli
authors: O
authors: Eskola
authors: Tove J
authors: TJ
authors: Grönroos
authors: Sarita
authors: S
authors: Forsback
authors: Johanna
authors: J
authors: Tuomela
authors: Gaber
authors: G
authors: Komar
authors: Jörgen
authors: J
authors: Bergman
authors: Pirkko
authors: P
authors: Härkönen
authors: Merja
authors: M
authors: Haaparanta
authors: Heikki
authors: H
authors: Minn
authors: Olof
authors: O
authors: Solin
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D017341:Etanidazole / Q000031:analogs & derivatives* / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D007536:Isomerism; D008297:Male; D051379:Mice; D011849:Radioactive Tracers; D051381:Rats; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays; D005466:Fluorocarbons
chemical_list: D017341:Etanidazole; D005462:Fluorine Radioisotopes; D006845:Hydrocarbons, Fluorinated; D011849:Radioactive Tracers; C096011:2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide; D005466:Fluorocarbons