PurposeThe aim of this study was to explore the cerebral distribution of the tau-specific PET tracer [18F]THK5317 (also known as (S)-[18F]THK5117) retention in different stages of Alzheimer’s disease; and study any associations with markers of hypometabolism and amyloid-beta deposition.MethodsThirty-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 [18F]THK5317, [11C] Pittsburgh compound B ([11C]PIB), and [18F]FDG were used to assess tau pathology, amyloid-beta deposition and cerebral glucose metabolism, respectively. The MCI patients were further divided into MCI [11C]PIB-positive (n = 11) and MCI [11C]PIB-negative (n = 2) groups.ResultsTest-retest variability for [18F]THK5317-PET was very low (1.17–3.81 %), as shown by retesting five patients. The patients with prodromal (MCI [11C]PIB-positive) and dementia-stage Alzheimer’s disease had significantly higher [18F]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 [18F]THK5317 retention and [18F]FDG uptake were observed mainly in the frontal cortex, and focal positive correlations were found between [18F]THK5317 and [11C]PIB retentions isocortically. One patient with corticobasal degeneration syndrome and one with progressive supranuclear palsy showed no [11C]PIB but high [18F]THK5317 retentions with a different regional distribution from that in Alzheimer’s disease patients.ConclusionsThe tau-specific PET tracer [18F]THK5317 images in vivo the expected regional distribution of tau pathology. This distribution contrasts with the different patterns of hypometabolism and amyloid-beta deposition.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-016-3363-z) contains supplementary material, which is available to authorized users.

The development of tau-specific positron emission tomography (PET) tracers allows imaging in vivo the regional load of tau pathology in Alzheimer's disease (AD) and other tauopathies. Eighteen patients with baseline investigations enroled in a 17-month follow-up study, including 16 with AD (10 had mild cognitive impairment and a positive amyloid PET scan, that is, prodromal AD, and six had AD dementia) and two with corticobasal syndrome. INTRODUCTIONThe aggregation of abnormally hyperphosphorylated tau protein into paired helical filaments is a key aspect of the pathology of Alzheimer's disease (AD). 1 Both the regional distribution of tau pathology in the brains of patients with AD and the sequential staging of its progression have been extensively described in postmortem studies. 2-5 These studies indicated, for the first time, that an early and relatively long preclinical phase of tau aggregation precedes the symptomatic stages of AD. 6,7 Despite this, the time course of tau pathology propagation, especially in relation to changes in the concomitant clinical and cognitive profiles of the individual patients, remains largely speculative because of the inherent limitations of post-mortem studies.During the past 5 years, the development of tau-specific positron emission tomography (PET) tracers 8 has provided a valuable addition to the neuroimaging arsenal. THK5317 [(S)-THK5117], a well characterised tau-specific tracer, 9-11 showed high retention in patients with AD with a regional pattern matching that of the distribution of tau pathology described by post-mortem studies. 12 Cross-sectionally, high load of tau pathology, as measured with THK5317 PET, was associated with