title: PET Quantification of Tau Pathology in Human Brain with 11C-PBB3.
abstract: Tau accumulation in the brain is a pathologic hallmark of Alzheimer disease and other tauopathies. Quantitative visualization of tau pathology in humans can be a powerful method as a diagnostic aid and for monitoring potential therapeutic interventions. We established methods of PET quantification of tau pathology with (11)C-PBB3 (2-((1E,3E)-4-(6-((11)C-methylamino)pyridin-3-yl)buta-1,3-dienyl) benzo[d]thiazol-6-ol), considering its radiometabolite entering the brain.
  
  
  METHODS
  Seven Alzheimer disease patients and 7 healthy subjects underwent dynamic (11)C-PBB3 PET scanning. Arterial blood was sampled to obtain the parent and metabolite input functions. Quantification of (11)C-PBB3 binding was performed using dual-input models that take the brain metabolite activity into consideration, traditional single-input models without such considerations, and the reference tissue model (MRTMO) and standardized uptake value ratio (SUVR). The cerebellar cortex was used as the reference tissue for all methods.
  
  
  RESULTS
  The dual-input graphical models estimated binding parameter ([Formula: see text]) stably (∼0.36 in high-binding regions). The MRTMO [Formula: see text] matched the corresponding [Formula: see text] by the dual-input graphical model (r(2) = 1.00). SUVR minus 1 correlated well with MRTMO [Formula: see text] (r(2) > 0.97). However, BPND by the single-input models did not correlate with [Formula: see text] by the dual-input graphical model (r(2) = 0.04).
  
  
  CONCLUSIONS
  The dual-input graphical model [Formula: see text] is consistent with the reference tissue [Formula: see text] and SUVR-1, suggesting that these parameters can accurately quantify binding of (11)C-PBB3 despite the entry of its radiometabolites into the brain.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and y-kimura@nirs.go.jp ichisem@nirs.go.jp.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and y-kimura@nirs.go.jp ichisem@nirs.go.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ichise
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and Advanced Clinical Research Center, Fukushima Medical University, Fukushima, Japan.
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: Yoko
authors.initials: Y
authors.lastname: Ikoma
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: Harumasa
authors.initials: H
authors.lastname: Takano
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kitamura
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: Kazunori
authors.initials: K
authors.lastname: Kawamura
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Naruhiko
authors.initials: N
authors.lastname: Sahara
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
authors.forename: Makoto
authors.initials: M
authors.lastname: Higuchi
mesh_terms: D000368:Aged; D000465:Algorithms; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D000631:Aminopyridines; D052160:Benzothiazoles; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D008954:Models, Biological; D057054:Molecular Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C000592806:2-(4-(6-(methylamino)pyridin-3-yl)buta-1,3-dienyl)benzo(d)thiazol-6-ol; D000631:Aminopyridines; D052160:Benzothiazoles; D019275:Radiopharmaceuticals; D016875:tau Proteins
keywords: 11C-PBB3; Alzheimer disease; PET quantification; tau