title: Comparison of 2beta-carbomethoxy-3beta-(4-[18F]fluorophenyl)tropane and N-(3-[18F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane, tracers for imaging dopamine transporter in rat.
abstract: OBJECTIVE
  This study compares 2beta-carbomethoxy-3beta-(4-[(18)F]fluorophenyl)tropane ([(18)F]beta-CFT) and N-(3-[(18)F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane ([(18)F]beta-CFT-FP) as radiotracers for imaging the dopamine transporter (DAT) in rat.
  
  
  METHODS
  Biodistribution, specificity and selectivity of the radiotracers were studied ex vivo in rats pre-treated with specific antagonists for DAT, serotonin transporter (SERT) and noradrenalin transporter (NET) and in control rats. Positron emission tomography (PET) studies were performed using an HRRT scanner. Radiolabelled metabolites were analyzed with thin-layer chromatography.
  
  
  RESULTS
  [(18)F]beta-CFT showed slow kinetics with a maximum striatum/cerebellum uptake ratio of 9.2 at 120 min. [(18)F]beta-CFT-FP showed fast kinetics with a maximum ratio of 3.1 at 5 min. Both tracers bound to DAT. [(18)F]beta-CFT also bound to NET. [(18)F]beta-CFT was more resistant to metabolism than [(18)F]beta-CFT-FP.
  
  
  CONCLUSIONS
  Structural modifications of [(18)F]beta-CFT significantly changed its biological properties, as shown by [(18)F]beta-CFT-FP. [(18)F]beta-CFT is a suitable tracer for both preclinical and human PET studies, but [(18)F]beta-CFT-FP is less suitable as a PET tracer.
authors: MediCity/PET Preclinical Laboratory, Turku PET Centre, University of Turku, Tykistökatu 6A, FI-20520, Turku, Finland. paivi.marjamaki@utu.fi
authors: Päivi
authors: P
authors: Marjamäki
authors: Merja
authors: M
authors: Haaparanta
authors: Sarita
authors: S
authors: Forsback
authors: Veronica
authors: V
authors: Fagerholm
authors: Olli
authors: O
authors: Eskola
authors: Tove
authors: T
authors: Grönroos
authors: Teija
authors: T
authors: Koivula
authors: Olof
authors: O
authors: Solin
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D009662:Nortropanes / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution; D014326:Tropanes / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: C552177:2beta-carbomethoxy-3beta-(4-(18F)fluorophenyl)tropane; D050483:Dopamine Plasma Membrane Transport Proteins; C552178:N-(3-(18F)fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane; D009662:Nortropanes; D011849:Radioactive Tracers; D014326:Tropanes