title: Quantitative Analysis of Amyloid Deposition in Alzheimer Disease Using PET and the Radiotracer ¹¹C-AZD2184.
abstract: Characteristic neuropathologic changes in Alzheimer disease (AD) are amyloid-β deposits and neurofibrillary tangles. Recently, a new radioligand for amyloid senile plaques, (11)C-labeled 5-(6-{[tert-butyl(dimethyl)silyl]oxy}-1,3-benzothiazol-2-yl)pyridin-2-amine ((11)C-AZD2184), was developed, and it was reported to show rapid brain uptake followed by rapid washout. In this study, (11)C-AZD2184 binding in control subjects and AD patients was examined in more detail by compartment model analysis using a metabolite-corrected arterial input function. The accuracy of simplified quantitative methods using a reference brain region was also evaluated.
  
  
  METHODS
  After intravenous bolus injection of (11)C-AZD2184, a dynamic PET scan was obtained for 90 min in 6 control subjects and 8 AD patients. To obtain the arterial input function, arterial blood sampling and high-performance liquid chromatography analysis were performed.
  
  
  RESULTS
  Time-activity curves in all brain regions could be described using the standard 2-tissue-compartment model. The total distribution volume ratios to reference region (DVR) in cerebral cortical regions were significantly higher in AD patients than in control subjects. Although there was no conspicuous accumulation of radioactivity in white matter as compared with other amyloid radioligands, DVR values in the centrum semiovale were more than 1 for both control subjects and AD patients, suggesting binding to myelin. The standardized uptake value ratio calculated from integrated time-activity curves in brain regions and the reference region was statistically in good agreement with DVR.
  
  
  CONCLUSIONS
  Although the white matter binding of (11)C-AZD2184 may have some effect on cortical measurement, it can be concluded that the kinetic behavior of (11)C-AZD2184 is suitable for quantitative analysis. The standardized uptake value ratio can be used as a validated measure of (11)C-AZD2184 binding in clinical examinations without arterial input function.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and hito@nirs.go.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimada
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shinotoh
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Harumasa
authors.initials: H
authors.lastname: Takano
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nogami
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Nagashima
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Takahata
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Chie
authors.initials: C
authors.lastname: Seki
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Kodaka
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Eguchi
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Hirano
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ikoma
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Makoto
authors.initials: M
authors.lastname: Higuchi
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawamura
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Fukumura
authors.affiliation: AstraZeneca Translational Sciences Center, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Éva Lindström
authors.initials: ÉL
authors.lastname: Böö
authors.affiliation: AstraZeneca Translational Sciences Center, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Farde
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000503:physiopathology; D000631:Aminopyridines / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism*; D001158:Arteries / Q000503:physiopathology; D052160:Benzothiazoles / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D049268:Positron-Emission Tomography
chemical_list: C539976:2-(6-(methylamino)pyridin-3-yl)-1,3-benzothiazol-6-ol; D000631:Aminopyridines; D000682:Amyloid; D052160:Benzothiazoles
keywords: AZD2184; Alzheimer; PET; amyloid