Abstract

Tau accumulation is known to be core pathologic changes in various neurodegenerative diseases including Alzheimer disease (AD) and frontotemporal dementia (FTD). Recently, [18F]AV-1451 (AV-1451) and [18F]THK5351 (THK5351) have been developed to detect tau deposition in vivo. We determined whether amount and distribution of THK5351 and AV-1451 cortical uptakes differed between AD and FTD cases. We also examined whether THK5351 and AV-1451 tracers exhibited different amounts and distribution of off-target bindings. Eight participants underwent magnetic resonance image, Florbetaben (FBB) and tau PET a using two tracers, THK5351 and AV-1451. Case 1 and 2 were clinically diagnosed as AD such as early onset AD and logopenic variant primary progressive aphasia (lvPPA). Case 3, 4, 5 and 6 were clinically diagnosed as FTD such as semantic variant primary progressive aphasia (svPPA), non-fluent/agrammatic variant PPA (nfvPPA) and behavioral variant FTD (bvFTD). Case 7 and 8 were normal control (NC). AV-1451 cortical uptakes were more prominent than THK5351 in Alzheimer disease, while, THK5351 cortical uptakes were more prominent in frontotemporal dementia, although THK5351 and AV-1451 tracers were highly correlated each other, (AD: r=0.63, p=0.009; FTD r=0.69, p<0.001). Off target bindings of THK5351 uptakes were more prominent than AV-1451 uptakes with cortical uptakes of AV-1451 were more striking in AD, while cortical uptakes of THK5351 were more prominent in FTD. Both THK5351 and AV-1451 tracers, regardless of type of dementia, showed off-target bindings in the midbrain, basal ganglia and thalamus, but THK5351 seemed more noticeable with high correlation (r= 0.61 to 0.98). AD cases showed higher cortical uptakes of AV-1451 than those of THK5351 while FTD cases showed higher cortical uptakes of THK5351 than those of AV-1451. Off target regions such as the midbrain, thalamus, and basal ganglia showed more prominent uptakes of THK5351than those of AV-1451 with wider variation of uptakes of THK5351. Our preliminary results suggested that AV-1451 seemed to be more sensitive and specific to Alzheimer disease type tau and less likely to present off-target binding.

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