title: Simplified quantification of nicotinic receptors with 2[18F]F-A-85380 PET.
abstract: BACKGROUND
  Neuronal nicotinic acetylcholine receptors (nAChRs), widely distributed in the human brain, are implicated in various neurophysiological processes as well as being particularly affected in neurodegenerative conditions such as Alzheimer's disease. We sought to evaluate a minimally invasive method for quantification of nAChR distribution in the normal human brain, suitable for routine clinical application, using 2[(18)F]F-A-85380 and positron emission tomography (PET).
  
  
  METHODS
  Ten normal volunteers (four females and six males, aged 63.40+/-9.22 years) underwent a dynamic 120-min PET scan after injection of 226 MBq 2[(18)F]F-A-85380 along with arterial blood sampling. Regional binding was assessed through standardized uptake value (SUV) and distribution volumes (DV) obtained using both compartmental (DV(2CM)) and graphical analysis (DV(Logan)). A simplified approach to the estimation of DV (DV(simplified)), defined as the region-to-plasma ratio at apparent steady state (90-120 min post injection), was compared with the other quantification approaches.
  
  
  RESULTS
  DV(Logan) values were higher than DV(2CM). A strong correlation was observed between DV(simplified), DV(Logan) (r=.94) and DV(2CM) (r=.90) in cortical regions, with lower correlations in thalamus (r=.71 and .82, respectively). Standardized uptake value showed low correlation against DV(Logan) and DV(2CM).
  
  
  CONCLUSIONS
  DV(simplified) determined by the ratio of tissue to metabolite-corrected plasma using a single 90- to 120-min PET acquisition appears acceptable for quantification of cortical nAChR binding with 2[(18)F]F-A-85380 and suitable for clinical application.
authors: Department of Nuclear Medicine and Centre for PET, Austin Hospital, Victoria 3084, Melbourne, Australia.
authors: Sascha
authors: S
authors: Mitkovski
authors: Victor L
authors: VL
authors: Villemagne
authors: Kathy E
authors: KE
authors: Novakovic
authors: Graeme
authors: G
authors: O'Keefe
authors: Henri
authors: H
authors: Tochon-Danguy
authors: Rachel S
authors: RS
authors: Mulligan
authors: Kerryn L
authors: KL
authors: Dickinson
authors: Tim
authors: T
authors: Saunder
authors: Marie-Claude
authors: MC
authors: Gregoire
authors: Michel
authors: M
authors: Bottlaender
authors: Frederic
authors: F
authors: Dolle
authors: Christopher C
authors: CC
authors: Rowe
mesh_terms: D001384:Azetidines / Q000493:pharmacokinetics; D001800:Blood Specimen Collection; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C119803:2-fluoro-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D005462:Fluorine Radioisotopes; D011725:Pyridines; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic