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P1‐245: Diffusion Kurtosis Image Analysis Associated with TAU Accumulation Measured by [ 18 F] THK‐5351 in Alzheimer’s Disease
Author(s) -
Imabayashi Etsuko,
Rokicki Jaroslav,
Kato Koichi,
Ogawa Masayo,
Matsuda Hiroshi
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.994
Subject(s) - fractional anisotropy , diffusion mri , white matter , diffusion imaging , nuclear medicine , kurtosis , medicine , magnetic resonance imaging , radiology , mathematics , statistics
bodies made against amyloid plaque (6E10) and NFTs (PHF6 & AT8) with brain slices adjacent to those of ARG study. Results: In AD brain slices, [H]MK-6240 binds AD tauopathy brain regions showing abundant NFTs. [H]MK-6240 binding is inhibited by self-block and T-808, but not by PIB. [H]MK-6240 binding patterns in NFT-rich AD brain slices are similar to IHC stain patterns of NFTs from the adjacent tissue slices. In non-AD brain slices, [H]MK-6240 exhibits minimal binding while [H]AV-1451 displays dense displaceable binding in the gray matter of cortex and hippocampus by self-block, but not by T-808. In tissue homogenate binding assays, [H]MK-6240 shows great binding potential (Bmax/Kd 1⁄4 226) in NFT-rich AD brain cortex by selfblock. [H]MK-6240 binds to one site with high affinity (Kd 1⁄4 0.286 0.09 nM). In non-AD brain cortex, [H]MK-6240 displays minimal non-saturable binding. In contrast, [H]-AV-1451 binds to more than one site in AD brain and shows displaceable binding in non-AD brain. Clorgyline inhibits [H]AV-1451 but not MK6240 binding in non-AD brain cortex (Ki1⁄4 0.43 nM). Conclusions: The study demonstrates [H]MK-6240 is a selective tau PET tracer with great binding potential and minimal non-specific binding in human AD brains. The data supports further development of MK-6240 as a tau-selective PET tracer.