title: [18F]CFT synthesis and binding to monoamine transporters in rats.
abstract: BACKGROUND
  We present the electrophilic synthesis of [18F]2β-carbomethoxy-3β-(4-fluoro)tropane [[18F]CFT] and the pharmacological specificity and selectivity of [18F]CFT for monoamine transporters in the brain and peripheral organs of rats. The human radiation dose is extrapolated from the animal data.
  
  
  METHODS
  [18F]CFT was synthesized by electrophilic fluorination of a stannylated precursor by using post-target-produced [18F]F2 as a fluorinating agent. The ex vivo 18F-activity biodistribution of [18F]CFT in the brain of rats was studied by autoradiography. The binding of [18F]CFT to the monoamine transporters was studied using in vivo blocking experiments with dopamine transporter [DAT], norepinephrine transporter [NET], or serotonin transporter [SERT] inhibitors. In vivo animal positron emission tomography was used as a comparative method to determine tracer kinetics. Human radiation dose was assessed using OLINDA software.
  
  
  RESULTS
  The radiochemical yield of [18F]CFT from the initial [18F]F-, decay corrected to the end of bombardment, was 3.2 ± 1.0%. The specific activity [SA] was 14.5 ± 3.4 GBq/μmol, decay corrected to the end of synthesis. Radiochemical purity exceeded 99%. DAT-specific binding was found in the striatum, locus coeruleus, and pancreas. NET-specific binding was found in the locus coeruleus. SERT-specific binding was not found in any of the studied organs. Effective dose equivalent [EDE] estimated for the standard human model was 12.8 μSv/MBq. Effective dose [ED] was 9.17 μSv/MBq.
  
  
  CONCLUSIONS
  Post-target-produced high-SA [18F]F2 was used to incorporate18F directly into the phenyl ring of [18F]CFT. The final product had high radiochemical and chemical purities and a high SA for DAT and NET studies in vivo. In periphery, [18F]CFT showed a specific uptake in the pancreas. EDE and ED corresponded well with other18F-radioligands.
authors.affiliation: Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Porthaninkatu 3, Turku, 20500, Finland. sarita.forsback@utu.fi.
authors.forename: Sarita
authors.initials: S
authors.lastname: Forsback
authors.forename: Päivi
authors.initials: P
authors.lastname: Marjamäki
authors.forename: Olli
authors.initials: O
authors.lastname: Eskola
authors.forename: Jörgen
authors.initials: J
authors.lastname: Bergman
authors.forename: Johanna
authors.initials: J
authors.lastname: Rokka
authors.forename: Tove
authors.initials: T
authors.lastname: Grönroos
authors.forename: Merja
authors.initials: M
authors.lastname: Haaparanta
authors.forename: Olof
authors.initials: O
authors.lastname: Solin