Abstract
Background[18F]THK5351, a recently-developed positron emission tomography (PET) tracer for measuring tau neurofibrillary tangle accumulation, may help researchers examine aging, disease, and tau pathology in living human brains. We examined THK5351 tracer pharmacokinetics to define an optimal acquisition time for static late images.MethodsPrimary measurements were calculation of regional values of distribution volume ratios (DVR) and standardized uptake value ratios (SUVR) in 6 healthy older control and 10 Alzheimer’s disease (AD) participants. We examined associations between DVR and SUVR, searching for a 20 min SUVR time window that was stable and comparable to DVR. We additionally examined diagnostic group differences in this 20 min SUVR.ResultsIn healthy controls, [18F]THK5351 uptake was low, with increased temporal relative to frontal binding. In AD, regional uptake was substantially higher than in healthy controls, with temporal exceeding frontal binding. Retention in cerebellar gray matter, which was used as the reference region, was low compared to other regions. Both DVR and SUVR values showed minimal change over time after 40 min. SUVR 20–40, 30–50, and 40–60 min were most consistently correlated with DVR; SUVR 40–60 min, the most stable time window, was used in further analyses. Significant (AD > healthy control) group differences existed in temporoparietal regions, with marginal medial temporal differences. We found high basal ganglia SUVR 40–60 min signal, with no group differences.ConclusionsWe examined THK5351, a new PET tracer for measuring tau accumulation, and compared multiple analysis methods for quantifying regional tracer uptake. SUVR 40–60 min performed optimally when examining 20 min SUVR windows, and appears to be a practical method for quantifying relative regional tracer retention. The results of this study offer clinical potential, given the usefulness of THK5351-PET as a biomarker of tau pathology in aging and disease.
Highlights
Tau pathology is frequently present in the brains of older adults, in the presence of Alzheimer’s Disease (AD) [1], and among cognitively normal older adults [2]
standardized uptake value ratios (SUVR) 20–40, 30–50, and 40–60 min were most consistently correlated with distribution volume ratios (DVR); SUVR 40–60 min, the most stable time window, was used in further analyses
The results of this study offer clinical potential, given the usefulness of THK5351-positron emission tomography (PET) as a biomarker of tau pathology in aging and disease
Summary
Tau pathology is frequently present in the brains of older adults, in the presence of Alzheimer’s Disease (AD) [1], and among cognitively normal older adults (potentially as primary age-related tauopathy or PART) [2]. There has recently been substantial progress in the development of radioligand tracers for studying the accumulation of tau pathology in the living human brain with positron emission tomography (PET) [9,10]. These developments come on the heels of major breakthroughs in our ability to image aggregated proteins associated with human disease; β-amyloid imaging was the first example of this. These tau radiotracers include FDDNP [11], T807/AV-1451 [12], and PBB3 [13]. We examined the pharmacokinetics and patterns of THK5351 uptake, and putative tau accumulation, in AD participants and in healthy control (HC) participants, to provide a more thorough understanding of this tracer, and potential processing and analysis considerations for any future researchers using this or related tracers
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