title: In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18).
abstract: An (18)F-labeled PET amyloid-beta (Abeta) imaging agent could facilitate the clinical evaluation of late-life cognitive impairment by providing an objective measure for Alzheimer disease (AD) pathology. Here we present the results of a clinical trial with (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine ((18)F-AV-45 or florbetapir [corrected] F 18).
  
  
  METHODS
  An open-label, multicenter brain imaging, metabolism, and safety study of (18)F-AV-45 was performed on 16 patients with AD (Mini-Mental State Examination score, 19.3 +/- 3.1; mean age +/- SD, 75.8 +/- 9.2 y) and 16 cognitively healthy controls (HCs) (Mini-Mental State Examination score, 29.8 +/- 0.45; mean age +/- SD, 72.5 +/- 11.6 y). Dynamic PET was performed over a period of approximately 90 min after injection of the tracer (370 MBq [10 mCi]). Standardized uptake values and cortical-to-cerebellum standardized uptake value ratios (SUVRs) were calculated. A simplified reference tissue method was used to generate distribution volume ratio (DVR) parametric maps for a subset of subjects.
  
  
  RESULTS
  Valid PET data were available for 11 AD patients and 15 HCs. (18)F-AV-45 accumulated in cortical regions expected to be high in Abeta deposition (e.g., precuneus and frontal and temporal cortices) in AD patients; minimal accumulation of the tracer was seen in cortical regions of HCs. The cortical-to-cerebellar SUVRs in AD patients showed continual substantial increases through 30 min after administration, reaching a plateau within 50 min. The 10-min period from 50 to 60 min after administration was taken as a representative sample for further analysis. The cortical average SUVR for this period was 1.67 +/- 0.175 for patients with AD versus 1.25 +/- 0.177 for HCs. Spatially normalized DVRs generated from PET dynamic scans were highly correlated with SUVR (r = 0.58-0.88, P < 0.005) and were significantly greater for AD patients than for HCs in cortical regions but not in subcortical white matter or cerebellar regions. No clinically significant changes in vital signs, electrocardiogram, or laboratory values were observed.
  
  
  CONCLUSIONS
  (18)F-AV-45 was well tolerated, and PET showed significant discrimination between AD patients and HCs, using either a parametric reference region method (DVR) or a simplified SUVR calculated from 10 min of scanning 50-60 min after (18)F-AV-45 administration.
authors.affiliation: Division of Nuclear Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-0807, USA. dfwong@jhmi.edu
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.forename: Paul B
authors.initials: PB
authors.lastname: Rosenberg
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Vanessa
authors.initials: V
authors.lastname: Raymont
authors.forename: Hayden T
authors.initials: HT
authors.lastname: Ravert
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
authors.forename: Ayon
authors.initials: A
authors.lastname: Nandi
authors.forename: James R
authors.initials: JR
authors.lastname: Brasić
authors.forename: Weiguo
authors.initials: W
authors.lastname: Ye
authors.forename: John
authors.initials: J
authors.lastname: Hilton
authors.forename: Constantine
authors.initials: C
authors.lastname: Lyketsos
authors.forename: Hank F
authors.initials: HF
authors.lastname: Kung
authors.forename: Abhinay D
authors.initials: AD
authors.lastname: Joshi
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Skovronsky
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pontecorvo
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds / Q000009:adverse effects / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D016022:Case-Control Studies; D064420:Drug-Related Side Effects and Adverse Reactions; D005026:Ethylene Glycols / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D011874:Radiometry; D014916:Whole-Body Irradiation
chemical_list: D000682:Amyloid; D000814:Aniline Compounds; D005026:Ethylene Glycols; D005462:Fluorine Radioisotopes; C545186:florbetapir