title: Quantitative kinetic analysis of PET amyloid imaging agents [(11)C]BF227 and [(18)F]FACT in human brain.
abstract: BACKGROUND
  The purpose of this study was to compare two amyloid imaging agents, [(11)C]BF227 and [(18)F]FACT (derivative from [(11)C]BF227) through quantitative pharmacokinetics analysis in human brain.
  
  
  METHODS
  Positron emission tomography studies were performed on six elderly healthy control (HC) subjects and seven probable Alzheimer's disease (AD) patients with [(11)C]BF227 and 10 HC subjects and 10 probable AD patients with [(18)F]FACT. Data from nine regions of interest were analyzed by several approaches, namely non-linear least-squared fitting methods with arterial input functions (one-tissue compartment model(1TCM), two-tissue compartment model (2TCM)), Logan plot, and linearized methods with reference region (Reference Logan plot (RefLogan), MRTM0, MRTM2). We also evaluated SUV and SUVR for both tracers. The parameters estimated by several approaches were compared between two tracers for detectability of differences between HC and AD patients.
  
  
  RESULTS
  For [(11)C]BF227, there were no significant difference of VT (2TCM, 1TCM) and SUV in all regions (Student t-test; p<0.05) and significant differences in the DVRs (Logan, RefLogan, and MRTM2) and SUVRs in six neocortical regions (p<0.05) between the HC and AD groups. For [(18)F]FACT, significant differences in DVRs (RefLogan, MRTM0, and MRTM2) were observed in more than four neocortical regions between the HC and AD groups (p<0.05), and the significant differences were found in SUVRs for two neocortical regions (inferior frontal coretex and lateral temporal coretex). Our results showed that both tracers can clearly distinguish between HC and AD groups although the pharmacokinetics and distribution patterns in brain for two tracers were substantially different.
  
  
  CONCLUSIONS
  This study revealed that although the PET amyloid imaging agents [(11)C]BF227 and [(18)F]FACT have similar chemical and biological properties, they have different pharmacokinetics, and caution must be paid for usage of the tracers.
authors.affiliation: Division of Medical Physics, Tohoku University School of Medicine, Sendai, Japan; Division of Cyclotron Nuclear Medicine, Cyclotron Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Shidahara
authors.affiliation: Division of Radiation Protection and Safety Control, Cyclotron Radioisotope Center, Tohoku University, Sendai, Japan. Electronic address: hwatabe@m.tohoku.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watabe
authors.affiliation: Division of Cyclotron Nuclear Medicine, Cyclotron Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Tashiro
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okamura
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Furumoto
authors.affiliation: Division of Cyclotron Nuclear Medicine, Cyclotron Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Watanuki
authors.affiliation: Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Division of Medical Physics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Arakawa
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Funaki
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Ren
authors.initials: R
authors.lastname: Iwata
authors.affiliation: Division of Medical Physics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Gonda
authors.affiliation: Division of Neuro-Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Yukitsuka
authors.initials: Y
authors.lastname: Kudo
authors.affiliation: Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.affiliation: Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001583:Benzoxazoles / Q000493:pharmacokinetics*; D003198:Computer Simulation; D006801:Humans; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D057054:Molecular Imaging / Q000379:methods*; D019579:Neocortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013844:Thiazoles / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: C000593009:2-((2-(2-(2-(dimethylamino)-1,3-thiazol-5-yl)vinyl)-1,3-benzoxazol-6-yl)oxy)-3-fluoropropan-1-ol; C516779:2-(2-(2-dimethylaminothiazol-5-yl)ethenyl)-6-(2-(fluoro)ethoxy)benzoxazole; D016229:Amyloid beta-Peptides; D001583:Benzoxazoles; D019275:Radiopharmaceuticals; D013844:Thiazoles
keywords: Amyloid imaging; Compartment model; [(11)C]BF227; [(18)F]FACT