In vivo selective imaging of tau pathology in Alzheimer's disease with ¹⁸F-THK5117

Objectives PET imaging of tau pathology would be useful for early and accurate diagnosis of dementia, tracking disease progression and evaluating treatment efficacy of anti-tau drugs. We have developed a novel PET tracer ¹⁸F-THK5117 that labels neurofibrillary tangles with high selectivity. To assess the clinical usefulness of this tracer, ¹⁸F-THK5117 PET studies were performed in healthy controls (HC) and Alzheimer's disease (AD) patients and compared with ¹¹C-PiB PET.

Methods 8 AD patients and 6 age-matched HC subjects underwent ¹⁸F-THK5117 PET scans for 90 min. ¹¹C-PiB PET scans were additionally performed in the same population. Standard uptake value ratios (SUVR) between 60-80 minutes post injection for THK5117 and SUVR between 40-70 minutes post injection for PiB were calculated using the cerebellar cortex as the reference region. Partial volume correction, accounting for both grey matter atrophy and white matter spill-over, was performed using PMOD 3.4 software.

Results AD patients showed ¹⁸F-THK5117 retention in the lateral and medial temporal cortices, areas known to contain high concentrations of tau deposits. ¹⁸F-THK5117 SUVR in these areas reached a plateau at 60 minutes post injection. Regional distribution of ¹⁸F-THK5117 differed considerably from that of ¹¹C-PiB in AD brains. ¹⁸F-THK5117 retention in the temporal cortex was correlated with the severity of dementia. In addition, ¹⁸F-THK5117 retention in the hippocampus was correlated with hippocampal volume in AD patients. Intriguingly, ¹⁸F-THK5117 retention in the right temporal lobe was observed in HC subject with right temporal lobe atrophy.

Conclusions ¹⁸F-THK5117 appears to selectively detect tau pathology in AD patients. This tracer could be employed to study longitudinal tau deposition in healthy aging and pathological conditions.

Research Support Supported in part by the research fund from GE Healthcare, the Industrial Technology Research Grant Program of the NEDO, Health and Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare, and the ‘Japan Advanced Molecular Imaging Program (J-AMP)’ of the Ministry of Education, Culture, Sports, Science, and Technology of Japan.