title: Visualization of regional tau deposits using (3)H-THK5117 in Alzheimer brain tissue.
abstract: BACKGROUND
  The accumulation of neurofibrillary tangles, composed of aggregated hyperphosphorylated tau protein, starts spreading early in specific regions in the course of Alzheimer's disease (AD), correlating with the progression of memory dysfunction. The non-invasive imaging of tau could therefore facilitate the early diagnosis of AD, differentiate it from other dementing disorders and allow evaluation of tau immunization therapy outcomes. In this study we characterized the in vitro binding properties of THK5117, a tentative radiotracer for positron emission tomography (PET) imaging of tau brain deposits.
  
  
  RESULTS
  Saturation and competition binding studies of (3)H-THK5117 in post-mortem AD brain tissue showed the presence of multiple binding sites. THK5117 binding was significantly higher in hippocampal (p < 0.001) and temporal (p < 0.01) tissue homogenates in AD compared to controls. Autoradiography studies with (3)H-THK5117 was performed on large frozen brain sections from three AD cases who had been followed clinically and earlier undergone in vivo (18)F-FDG PET investigations. The three AD cases showed distinct differences in regional THK5117 binding that were also observed in tau immunohistopathology as well as in clinical presentation. A negative correlation between in vivo (18)F-FDG PET and in vitro (3)H-THK5117 autoradiography was observed in two of the three AD cases.
  
  
  CONCLUSIONS
  This study supports that new tau PET tracers will provide further understanding on the role of tau pathology in the diversity of the clinical presentation in AD.
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Novum, 5th floor, Stockholm, S-14157, Sweden.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Lemoine
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Novum, 5th floor, Stockholm, S-14157, Sweden.
authors.forename: Laure
authors.initials: L
authors.lastname: Saint-Aubert
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Novum, 5th floor, Stockholm, S-14157, Sweden.
authors.forename: Amelia
authors.initials: A
authors.lastname: Marutle
authors.affiliation: Preclinical PET Platform, Department of Medicinal Chemistry, Faculty of Pharmacy, Uppsala University, Uppsala, Sweden.|PET Centre, Centre for Medical Imaging, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Antoni
authors.affiliation: Preclinical PET Platform, Department of Medicinal Chemistry, Faculty of Pharmacy, Uppsala University, Uppsala, Sweden.|PET Centre, Centre for Medical Imaging, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Jonas P
authors.initials: JP
authors.lastname: Eriksson
authors.affiliation: Department of Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okamura
authors.affiliation: Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Inger
authors.initials: I
authors.lastname: Nennesmo
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Novum, 5th floor, Stockholm, S-14157, Sweden.
authors.forename: Per-Göran
authors.initials: PG
authors.lastname: Gillberg
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Novum, 5th floor, Stockholm, S-14157, 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: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D000814:Aniline Compounds / Q000493:pharmacokinetics; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D011804:Quinolines / Q000493:pharmacokinetics; D013223:Statistics as Topic; D014316:Tritium / Q000493:pharmacokinetics; D016875:tau Proteins / Q000187:drug effects / Q000378:metabolism*
chemical_list: C000604726:6-((3-fluoro-2-hydroxy)propoxy)-2-(4-methylaminophenyl)quinoline; D000814:Aniline Compounds; D011804:Quinolines; D016875:tau Proteins; D019788:Fluorodeoxyglucose F18; D014316:Tritium