title: Imaging in-vivo tau pathology in Alzheimer's disease with THK5317 PET in a multimodal paradigm.
abstract: OBJECTIVE
  The aim of this study was to explore the cerebral distribution of the tau-specific PET tracer [(18)F]THK5317 (also known as (S)-[(18)F]THK5117) retention in different stages of Alzheimer's disease; and study any associations with markers of hypometabolism and amyloid-beta deposition.
  
  
  METHODS
  Thirty-three individuals were enrolled, including nine patients with Alzheimer's disease dementia, thirteen with mild cognitive impairment (MCI), two with non-Alzheimer's disease dementia, and nine healthy controls (five young and four elderly). In a multi-tracer PET design [(18)F]THK5317, [(11)C] Pittsburgh compound B ([(11)C]PIB), and [(18)F]FDG were used to assess tau pathology, amyloid-beta deposition and cerebral glucose metabolism, respectively. The MCI patients were further divided into MCI [(11)C]PIB-positive (n = 11) and MCI [(11)C]PIB-negative (n = 2) groups.
  
  
  RESULTS
  Test-retest variability for [(18)F]THK5317-PET was very low (1.17-3.81 %), as shown by retesting five patients. The patients with prodromal (MCI [(11)C]PIB-positive) and dementia-stage Alzheimer's disease had significantly higher [(18)F]THK5317 retention than healthy controls (p = 0.002 and p = 0.001, respectively) in areas exceeding limbic regions, and their discrimination from this control group (using the area under the curve) was >98 %. Focal negative correlations between [(18)F]THK5317 retention and [(18)F]FDG uptake were observed mainly in the frontal cortex, and focal positive correlations were found between [(18)F]THK5317 and [(11)C]PIB retentions isocortically. One patient with corticobasal degeneration syndrome and one with progressive supranuclear palsy showed no [(11)C]PIB but high [(18)F]THK5317 retentions with a different regional distribution from that in Alzheimer's disease patients.
  
  
  CONCLUSIONS
  The tau-specific PET tracer [(18)F]THK5317 images in vivo the expected regional distribution of tau pathology. This distribution contrasts with the different patterns of hypometabolism and amyloid-beta deposition.
authors.affiliation: Department NVS, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Novum 5th floor, 141 57, Huddinge, Sweden.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Chiotis
authors.affiliation: Department NVS, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Novum 5th floor, 141 57, Huddinge, Sweden.
authors.forename: Laure
authors.initials: L
authors.lastname: Saint-Aubert
authors.affiliation: Department of Radiology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Irina
authors.initials: I
authors.lastname: Savitcheva
authors.affiliation: Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Vesna
authors.initials: V
authors.lastname: Jelic
authors.affiliation: Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Pia
authors.initials: P
authors.lastname: Andersen
authors.affiliation: Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.|Medical Physics, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: My
authors.initials: M
authors.lastname: Jonasson
authors.affiliation: PET Centre, Uppsala University Hospital, Uppsala, Sweden.|Pre-clinical PET Platform, Uppsala University, Uppsala, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Eriksson
authors.affiliation: Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.affiliation: Department NVS, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Novum 5th floor, 141 57, Huddinge, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.|Department of Psychology, Stockholm University, Stockholm, Sweden.
authors.forename: Ove
authors.initials: O
authors.lastname: Almkvist
authors.affiliation: Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.|PET Centre, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Wall
authors.affiliation: PET Centre, Uppsala University Hospital, Uppsala, Sweden.|Pre-clinical PET Platform, Uppsala University, Uppsala, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Antoni
authors.affiliation: Department NVS, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Novum 5th floor, 141 57, Huddinge, Sweden. Agneta.K.Nordberg@ki.se.|Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden. Agneta.K.Nordberg@ki.se.
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D011804:Quinolines / Q000378:metabolism; D011849:Radioactive Tracers; D055815:Young Adult
chemical_list: C000604726:6-((3-fluoro-2-hydroxy)propoxy)-2-(4-methylaminophenyl)quinoline; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D011804:Quinolines; D011849:Radioactive Tracers
keywords: Alzheimer’s disease; Amyloid PET; FDG; Neurofibrillary tangles; Non-AD; Other dementia; PIB; Positron emission tomography; THK5317; Tau