ObjectiveTo evaluate the effectiveness of a new tracer (S)-1-(4-(6-(dimethylamino)quinoxalin-2-yl)phenoxy)-3-fluoropropan-2-ol ([F-18]-S16), in distinguishing patients with AD from HCs. MethodsPaired [F-18]-S16 and [F-18]-THK5317 scans were acquired in five patients with AD, six HCs, one subject with a semantic variant of primary progressive aphasia (sv-PPA) and one subject with probable progressive supranuclear palsy (PSP). Dynamic PET scanning was performed over 90 min after injection of the tracers. Standardized uptake values (SUV) and cortical-to-cerebellum standardized uptake value ratios (SUVRs) were used for tau deposition semi-quantization. A voxel-based analysis was employed to assess the uptake difference between populations. Results[F-18]-S16 exhibited excellent blood-brain-barrier penetration. AD patients showed increased cortical [F-18]-THK5317 and [F-18]-S16 binding. Compared to HCs, AD patients showed significantly increased cortical [F-18]-S16 uptake in the bilateral occipital cortex, posterior cingulated cortex/precuneus, and lateral frontal cortex. Notable [F-18]-S16 uptake was observed in the basal ganglia and brainstem compared to the neocortex. A substantial [F-18]-S16 signal was detected in the basal ganglia and midbrain in a patient with probable PSP and in the bilateral anterior temporal cortex in a sv-PPA patient. Conclusion[F-18]-S16 might be of help to detect tau protein in vivo.