Fluorine-19 magnetic resonance imaging to detect tau pathology in rTg4510 mice

[Speaker] Daijiro Yanagisawa:1
[Co-author] Hiroyasu Taguchi:1, Shigehiro Morikawa:1, Ikuo Tooyama:1
1:Molecular Neuroscience Research Center, Shiga University of Medical Science, Japan

Abnormal hyperphosphorylaion and aggregation of tau into neurofibrillary tangles is characteristic of a wide range of neurodegenerative diseases known as tauopathies. Recent advances in neuroimaging techniques allow us to evaluate the tau pathology in the brain, so-called 'tau imaging', which may contribute to early diagnosis of high risk individuals and monitoring disease progress and the efficacy during drug treatment. Here we have developed a probe for tau imaging using fluorine-19 magnetic resonance imaging (MRI), and detected tau pathology in a mouse model of tauopathy. All experimental procedures in this study were approved by the Committee on Animal Care of Shiga University of Medical Science. We synthesized fluorine-19-labeled compound, a buta-1,3-diene derivative with PEG side chain bearing CF3 group, named Shiga-X35. Female rTg4510 mice and wild-type mice were intravenously injected with Shiga-X35, and MRI of each mouse head was conducted with a 7.0 T horizontal-bore magnetic resonance scanner. Brain sections were prepared after MRI, and fluorescence microscopic analysis was then performed. The fluorine-19 MRI in rTg4510 mice showed an intense signal in the forebrain region. Comparison of the signal intensity of fluorine-19 magnetic resonance in the forebrain region between rTg4510 mice and wild-type mice revealed a significant accumulation of fluorine-19 magnetic resonance signal in the rTg4510 mice, compared with the wild-type mice. Fluorescence microscopic analysis showed fluorescence signals of Shiga-X35 colocalized with phosphorylated tau in the brain of rTg4510 mice. These results suggest that fluorine-19 MRI detected Shiga-X35 that bound to pathological tau aggregates in the brain of rTg4510 mice. Data collected as part of this investigation indicate that fluorine-19 MRI using Shiga-X35 represent a promising tool to detect tau pathology in the brain.
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