Abstract
The availability of tau PET radioligands enables quantitative assessment of tau density and distribution in the human brain. We evaluated the kinetics of a novel radioligand, (18)F-RO-948 (previously referred to as (18)F-RO6958948), and its ability to identify tau positivity in individual patients with mild Alzheimer disease (AD). Methods: Eleven subjects with amyloid-positive mild AD, 5 amyloid-negative older control subjects (OC), and 5 younger control subjects (YC) completed 1 or 2 (4 AD and 5 OC) PET scans with (18)F-RO-948 for 90, 120, or 200 min. The kinetics of the radioligand was evaluated with standard compartmental and noncompartmental models (with plasma data in 70% of cases), tissue-reference methods, and SUV ratio. These approaches were applied to assess the ability of (18)F-RO-948 to discriminate AD subjects from OC subjects. Results: The plasma reference graphical analysis appeared to be the optimal method of quantification for (18)F-RO-948, yielding strictly time-consistent values of distribution volume and distribution volume ratio at 90 min against the analyses at 120 and 200 min. The reference tissue graphical analysis and SUV ratio were cross-validated against plasma reference graphical analysis. Test-retest evaluation showed excellent reproducibility. A proposed novel index of tau load, the regional tau-positive fraction, showed high values in the medial and lateral temporal and parietal regions in AD and successfully separated AD subjects from OC and YC subjects with a significant margin. Conclusion:(18)F-RO-948 appears to be a promising radioligand for quantitative imaging of tau in the brain of AD patients.