Neurofibrillary pathology containing microtubule-associated protein tau is one of the neuropathological hallmarks in Alzheimer's disease (AD). Non-invasive detection of neurofibrillary tangles in living subjects would provide not only clinical advantages such as diagnosis and treatment but also better understanding of pathophysiology in AD. We have developed arylquinoline derivatives as potential candidates for tau-selective PET tracers. The aim of study was to validate the clinical usefulness of [¹⁸F]THK-5117 as a tau-selective PET tracer. Methods: In vitro binding assays and autoradiography of THK-5117 were conducted using human brain tissues to validate the binding selectivity to neurofibrillary pathology, compared with amyloid PET tracer PiB. Clinical PET studies with [¹⁸F]THK-5117 and [¹¹C]PiB were conducted in fourteen participants including eight Alzheimer's patients and six healthy controls. Results: Selective binding of THK-5117 to neurofibrillary pathology was observed in post-mortem brain tissues from AD. In human PET study, patients with AD had increased [¹⁸F]THK-5117 retention compared to healthy subjects. Regional distribution of [¹⁸F]THK-5117 was similar to the pattern of neurofibrillary pathology typically seen in postmortem analyses of patients with AD, which was obviously different from that of [¹¹C]PiB. In addition, [¹⁸F]THK-5117 uptake in the mesial temporal cortex was correlated with hippocampal volume in AD patients. Conclusion: [¹⁸F]THK-5117 selectively binds to neurofibrillary pathology in AD patients, providing regional quantitative information on tau pathology in living subjects. In combination with amyloid PET imaging, non-invasive imaging of neurofibrillary pathology may shed light on the true nature of AD-related pathophysiology in humans.