Pharmacokinetic evaluation of the tau radiotracer [18F]T807

414 Objectives [18F]T807 was developed for PET imaging of tau protein aggregates which are implicated in Alzheimer’s disease and traumatic brain injury (TBI). The goal of this work was to provide an initial characterization of [18F]T807 pharmacokinetics using arterial input functions. Methods Four subjects (1 control, 1 MCI, 2 TBI) underwent [18F]T807 PET scans. Dynamic PET data were measured for 120 min after bolus injection of [18F]T807. Arterial blood sampling and radiometabolite analyses were performed. Dynamic PET images were warped to a standardized space using the subject’s MRI. Total volume of distribution (VT) was estimated using the Logan graphical method and one- (1CM) and two- (2CM) tissue compartment models. Results Whole blood:plasma ratio was close to unity by 1 minute (range: 0.85-1.1). Plasma parent fraction followed a single exponential (T1/2: 14.7±1.7 min); primarily polar metabolites were observed on HPLC. Metabolite corrected plasma activity fit a bi-exponential (T1/2: 208±76; 3.1±0.03 min). Plasma clearance was 146±50 ml/kg/hr. By 15 minutes, venous matched arterial concentrations within ~10%. [18F]T807 in gray matter peaked quickly (SUV >2 at ~5 minutes). Logan plots became linear no later than 30 min and voxelwise analysis gave high quality results. Compartmental models gave good fits but preferred model varied by region. VT was higher in the occipital lobe (OL) of the MCI subject (6.1) compared to control (4.4). OL preferred a 2CM as opposed to the cerebellum that preferred a 1CM. High focal uptake was found in the corpus callosum of the acute head injury subject compared to control (VT =5.3 vs. 4.6). Conclusions [18F]T807 showed rapid clearance from plasma and properties suitable for tau quantification with PET. Initial studies suggest that graphical and compartmental techniques are suitable for quantification. Future [18F]T807 scans with arterial sampling are scheduled and will provide a more thorough assessment of [18F]T807 kinetics. Research Support T32EB013180