Journal Article

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

Lubberink, Mark, Almkvist, Ove, Jelic, Vesna, Saint-Aubert, Laure, Jonasson, My, Eriksson, Jonas, Wall, Anders, Chiotis, Konstantinos, Antoni, Gunnar, Savitcheva, Irina, Andersen, Pia, Nordberg, Agneta

2016

Overview

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.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Adult / Aged / Alzheimer Disease - diagnostic imaging / Alzheimer Disease - metabolism / Alzheimer's disease / Amyloid beta-Peptides - metabolism / Amyloid PET / Aniline Compounds - metabolism / Cardiology / Case-Control Studies / FDG / Female / Humans / Imaging / Male / Medical imaging / Medicine / Medicine & Public Health / Middle Aged / Multimodal Imaging / Neurofibrillary tangles / Non-AD / Nuclear Medicine / Oncology / Original / Original Article / Orthopedics / Other dementia / Pathology / PIB / Positron emission tomography / Psychology / psykologi / Quinolines - metabolism / Radioactive Tracers / Radiology / Tau / THK5317 / Young Adult