title: Using PET with 18F-AV-45 (florbetapir) to quantify brain amyloid load in a clinical environment.
abstract: OBJECTIVE
  Positron emission tomography (PET) imaging of brain amyloid load has been suggested as a core biomarker for Alzheimer's disease (AD). The aim of this study was to test the feasibility of using PET imaging with (18)F-AV-45 (florbetapir) in a routine clinical environment to differentiate between patients with mild to moderate AD and mild cognitive impairment (MCI) from normal healthy controls (HC).
  
  
  METHODS
  In this study, 46 subjects (20 men and 26 women, mean age of 69.0 ± 7.6 years), including 13 with AD, 12 with MCI and 21 HC subjects, were enrolled from three academic memory clinics. PET images were acquired over a 10-min period 50 min after injection of florbetapir (mean ± SD of radioactivity injected, 259 ± 57 MBq). PET images were assessed visually by two individuals blinded to any clinical information and quantitatively via the standard uptake value ratio (SUVr) in the specific regions of interest, which were defined in relation to the cerebellum as the reference region.
  
  
  RESULTS
  The mean values of SUVr were higher in AD patients (median 1.20, Q1-Q3 1.16-1.30) than in HC subjects (median 1.05, Q1-Q3 1.04-1.08; p = 0.0001) in the overall cortex and all cortical regions (precuneus, anterior and posterior cingulate, and frontal median, temporal, parietal and occipital cortex). The MCI subjects also showed a higher uptake of florbetapir in the posterior cingulate cortex (median 1.06, Q1-Q3 0.97-1.28) compared with HC subjects (median 0.95, Q1-Q3 0.82-1.02; p = 0.03). Qualitative visual assessment of the PET scans showed a sensitivity of 84.6% (95% CI 0.55-0.98) and a specificity of 38.1% (95% CI 0.18-0.62) for discriminating AD patients from HC subjects; however, the quantitative assessment of the global cortex SUVr showed a sensitivity of 92.3% and specificity of 90.5% with a cut-off value of 1.122 (area under the curve 0.894).
  
  
  CONCLUSIONS
  These preliminary results suggest that PET with florbetapir is a safe and suitable biomarker for AD that can be used routinely in a clinical environment. However, the low specificity of the visual PET scan assessment could be improved by the use of specific training and automatic or semiautomatic quantification tools.
authors.affiliation: UMR INSERM U930-CNRS ERL 3106, Tours, France. vincent.camus@univ-tours.fr
authors.forename: V
authors.initials: V
authors.lastname: Camus
authors.forename: P
authors.initials: P
authors.lastname: Payoux
authors.forename: L
authors.initials: L
authors.lastname: Barré
authors.forename: B
authors.initials: B
authors.lastname: Desgranges
authors.forename: T
authors.initials: T
authors.lastname: Voisin
authors.forename: C
authors.initials: C
authors.lastname: Tauber
authors.forename: R
authors.initials: R
authors.lastname: La Joie
authors.forename: M
authors.initials: M
authors.lastname: Tafani
authors.forename: C
authors.initials: C
authors.lastname: Hommet
authors.forename: G
authors.initials: G
authors.lastname: Chételat
authors.forename: K
authors.initials: K
authors.lastname: Mondon
authors.forename: V
authors.initials: V
authors.lastname: de La Sayette
authors.forename: J P
authors.initials: JP
authors.lastname: Cottier
authors.forename: E
authors.initials: E
authors.lastname: Beaufils
authors.forename: M J
authors.initials: MJ
authors.lastname: Ribeiro
authors.forename: V
authors.initials: V
authors.lastname: Gissot
authors.forename: E
authors.initials: E
authors.lastname: Vierron
authors.forename: J
authors.initials: J
authors.lastname: Vercouillie
authors.forename: B
authors.initials: B
authors.lastname: Vellas
authors.forename: F
authors.initials: F
authors.lastname: Eustache
authors.forename: D
authors.initials: D
authors.lastname: Guilloteau
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds / Q000009:adverse effects; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging; D005026:Ethylene Glycols / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000009:adverse effects / Q000379:methods*
chemical_list: D000682:Amyloid; D000814:Aniline Compounds; D005026:Ethylene Glycols; C545186:florbetapir