[18F]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer's disease

Purpose Visualization of the spatial distribution of neurofibrillary tangles would help in the diagnosis, prevention and treatment of dementia. The purpose of the study was to evaluate the clinical utility of [F-18]THK-5117 as a highly selective tau imaging radiotracer. Methods We initially evaluated in vitro binding of [H-3]THK-5117 in post-mortem brain tissues from patients with Alzheimer's disease (AD). In clinical PET studies, [F-18]THK-5117 retention in eight patients with AD was compared with that in six healthy elderly controls. Ten subjects underwent an additional [C-11]PiB PET scan within 2 weeks. Results In post-mortem brain samples, THK-5117 bound selectively to neurofibrillary deposits, which differed from the binding target of PiB. In clinical PET studies, [F-18]THK-5117 binding in the temporal lobe clearly distinguished patients with AD from healthy elderly subjects. Compared with [C-11]PiB, [F-18]THK-5117 retention was higher in the medial temporal cortex. Conclusion These findings suggest that [F-18]THK-5117 provides regional information on neurofibrillary pathology in living subjects.