Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [ 18 F]MK6240 in human subjects

Purpose [ 18 F]MK6240 was developed for PET imaging of tau aggregates, which are implicated in Alzheimer’s disease. The goal of this work was to evaluate the kinetics of [ 18 F]MK6240 and to investigate different strategies for in-vivo quantification of tau aggregates in humans. Methods Thirty-five subjects, consisting of 18 healthy controls (CTRL), 11 subjects with mild cognitive impairment (MCI) and six with Alzheimer’s Disease (AD), underwent dynamic [ 18 F]MK6240 PET scans. Arterial blood measurements were collected in 16 subjects (eight CTRLs, six MCIs and two AD) to measure whole blood and plasma concentration time courses. Radiometabolite analysis was performed on a subset of plasma samples. Various compartmental model configurations as well as the Logan and multilinear analysis (MA1) graphical methods with arterial plasma input function were tested. Simplified reference tissue methods were investigated, including Logan distribution volume ratio (DVR), multilinear reference tissue method (MRTM2), and static SUV ratio using the cerebellum as a reference region. Results Whole blood:plasma ratio stabilized to 0.66 ± 0.01 after 15 min. Percent parent in plasma (