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Imaging in-vivo tau pathology in Alzheimer's disease with THK5317 PET in a multimodal paradigm
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2016 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, no 9, 1686-1699 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: 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.

Place, publisher, year, edition, pages
2016. Vol. 43, no 9, 1686-1699 p.
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-281916DOI: 10.1007/s00259-016-3363-zISI: 000379017500015PubMedID: 26996778OAI: oai:DiVA.org:uu-281916DiVA: diva2:915971
Funder
Swedish Research Council, 05817The Karolinska Institutet's Research FoundationStiftelsen Gamla TjänarinnorThe Swedish Brain FoundationThe Dementia Association - The National Association for the Rights of the DementedWenner-Gren FoundationsEU, European Research Council, HEALTH-F2-2011-278850Swedish Foundation for Strategic Research
Available from: 2016-03-31 Created: 2016-03-31 Last updated: 2017-11-30Bibliographically approved

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Jonasson, MyEriksson, JonasLubberink, MarkWall, AndersAntoni, Gunnar

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