Dynamic PET measures of tau accumulation in cognitively normal older adults and Alzheimer's disease patients measured using [18F] THK-5351

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. Methods: Primary 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. Results: In 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. Conclusions: We 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.