title: In vivo imaging of human cerebral nicotinic acetylcholine receptors with 2-18F-fluoro-A-85380 and PET.
abstract: 2-(18)F-fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine (2-(18)F-fluoro-A-85380) is a PET radioligand that is specific for nicotinic acetylcholine receptors (nAChRs) and has a high affinity for the alpha(4)beta(2) subtype. The purpose of this study was to evaluate different strategies to quantify 2-(18)F-fluoro-A-85380 binding in healthy nonsmoking human volunteers.
  
  
  METHODS
  After intravenous injection of 189 +/- 30 MBq (0.8-5.7 nmol) of 2-(18)F-fluoro-A-85380, the first dynamic PET scan was acquired over 150 min. The second 30-min PET scan was performed 60 min later. Time-activity curves were generated from volumes of interest. 2-(18)F-Fluoro-A-85380 volume of distribution (DV) was quantified using compartmental kinetic analysis and Logan graphical analysis. In the kinetic analysis, the 1-tissue compartment model (1TCM) and the 2-tissue (2TCM) compartment model were applied. The most appropriate kinetic model was determined using the Akaike Information Criterion. The effect of reducing the PET study duration on the reliability of the DV values computed by the kinetic and the graphical analyses was evaluated.
  
  
  RESULTS
  Time-activity curves were better described by the 2TCM. The DV values ranged from 5.2 +/- 0.5 in the occipital cortex, 6.2 +/- 0.2 in the frontal cortex, and 7.3 +/- 0.4 in the putamen to 15.4 +/- 2.1 in the thalamus. These regional DV values were consistent with the distribution of nAChRs in the human brain. Logan graphical analysis provided slightly lower DV values than those of the 2TCM (from -3.5% in the occipital cortex to -6.6% in the thalamus). The minimal study duration required to obtain stable DV estimates in all regions was similar for the 2 methods: 140 min for the 2TCM and 150 min for the Logan analysis. DV estimates obtained with the 2TCM were more stable than those calculated by the Logan approach for the same scan duration.
  
  
  CONCLUSIONS
  These results show that 2-(18)F-fluoro-A-85380 can be used to assess nAChRs binding in the human brain with PET.
authors.affiliation: Service Hospitalier Frédéric Joliot, Departement de Recherche Medicale/Direction des Sciences du Vivant, Commissariat à l'Energie Atomique, F-91406 Orsay, France.
authors.forename: Jean-Dominique
authors.initials: JD
authors.lastname: Gallezot
authors.forename: Michel
authors.initials: M
authors.lastname: Bottlaender
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Grégoire
authors.forename: Dimitri
authors.initials: D
authors.lastname: Roumenov
authors.forename: Jean-Robert
authors.initials: JR
authors.lastname: Deverre
authors.forename: Christine
authors.initials: C
authors.lastname: Coulon
authors.forename: Michèle
authors.initials: M
authors.lastname: Ottaviani
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dollé
authors.forename: André
authors.initials: A
authors.lastname: Syrota
authors.forename: Héric
authors.initials: H
authors.lastname: Valette
mesh_terms: D000328:Adult; D001384:Azetidines / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000493:pharmacokinetics*; D011865:Radioisotope Dilution Technique; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C119803:2-fluoro-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D011725:Pyridines; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic