title: Imaging characteristics and safety of florbetapir (¹⁸F) in Japanese healthy volunteers, patients with mild cognitive impairment and patients with Alzheimer's disease.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the performance characteristics and safety of florbetapir ((I8)F) positron emission tomography (PET) in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and cognitively normal (CN) control patients from Japan.
  
  
  METHODS
  Florbetapir ((I8)F) PET was obtained in 48 subjects (15 AD patients, 15 MCI patients, and 18 CNs) within a multicenter phase 2/3 study. Amyloid burden was assessed visually and classified as positive or negative for pathologic levels of amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVRs) were determined from the florbetapir ((I8)F) PET images. Safety was assessed by monitoring adverse events, vital signs, clinical laboratory assessments, and electrocardiograms. Demographic variables and cognitive scales were summarized by using descriptive statistics for each group. Fisher's exact test and one-way analysis of variance were used to compare amyloid positivity and mean SUVRs, respectively, between diagnostic groups.
  
  
  RESULTS
  Florbetapir ((I8)F) PET was rated visually amyloid positive in 80.0% of AD patients, 33.3% of MCI patients, and 16.7% of CNs. Mean SUVRs were highest in the AD group and lowest in the CN group for each brain region (P < 0.01) and globally (P < 0.05). Kappa statistics showed strong inter-reader agreement (Fleiss' kappa = 0.82) and individual reader's agreement with the majority of readers (kappa ranged from 0.79 to 1.0). Seventeen of the 48 subjects (35.4%) were Apolipoprotein E genotype ε4 positive, which included 10 subjects in the AD group and 7 subjects in the MCI group. A total of 6 subjects (5 of whom were in the CN group) had at least 1 treatment-emergent adverse event (TEAE).
  
  
  CONCLUSIONS
  These data indicate that amyloid positivity increased with diagnostic category (CN < MCI < AD) and are consistent with expected rates of amyloid positivity among individuals with clinical diagnoses of AD and MCI. In addition, these results were similar to those obtained in United States studies. Florbetapir ((18)F) was safe and well tolerated. The reliability of both qualitative and quantitative assessments of florbetapir ((18)F) in this study population provides support for potential use in clinical settings in Japan.
authors.affiliation: Department of Psychiatry, Kyoto University Hospital, 54 Kawaharacho, Syogoin, Sakyu-ku, Kyoto, 606-8507, Japan, cnamiki@kuhp.kyoto-u.ac.jp.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Namiki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Iwata
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Momose
authors.forename: Michio
authors.initials: M
authors.lastname: Senda
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Okubo
authors.forename: Abhinay D
authors.initials: AD
authors.lastname: Joshi
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Abigail
authors.initials: A
authors.lastname: Agbulos
authors.forename: Christopher
authors.initials: C
authors.lastname: Breault
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pontecorvo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D000814:Aniline Compounds; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging*; D005026:Ethylene Glycols; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000009:adverse effects* / Q000379:methods*; D012449:Safety
chemical_list: D000814:Aniline Compounds; D005026:Ethylene Glycols; C545186:florbetapir