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Eur J Nucl Med Mol Imaging. 2016 Aug;43(9):1686-99. doi: 10.1007/s00259-016-3363-z. Epub 2016 Mar 21.

Imaging in-vivo tau pathology in Alzheimer's disease with THK5317 PET in a multimodal paradigm.

Author information

1
Department NVS, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Novum 5th floor, 141 57, Huddinge, Sweden.
2
Department of Radiology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
3
Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
4
Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
5
Medical Physics, Uppsala University Hospital, Uppsala, Sweden.
6
PET Centre, Uppsala University Hospital, Uppsala, Sweden.
7
Pre-clinical PET Platform, Uppsala University, Uppsala, Sweden.
8
Department of Psychology, Stockholm University, Stockholm, Sweden.
9
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.
10
Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden. Agneta.K.Nordberg@ki.se.

Abstract

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.

KEYWORDS:

Alzheimer’s disease; Amyloid PET; FDG; Neurofibrillary tangles; Non-AD; Other dementia; PIB; Positron emission tomography; THK5317; Tau

PMID:
26996778
PMCID:
PMC4932128
DOI:
10.1007/s00259-016-3363-z
[Indexed for MEDLINE]
Free PMC Article

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