Presentation Abstract

Program#/Poster#: 551.20/D5
Presentation Title: In vitro binding analysis of THK523 to Aβ and tau protein fibrils
Location: Hall A-C
Presentation time: Tuesday, Nov 15, 2011, 11:00 AM -12:00 PM
1Dept Pharmacol, 2Dept Geriatrics and Gerontology, Tohoku Univ. Sch. Med., Sendai, Japan; 3Innovation of New Biomed. Engin. Ctr., Tohoku Univ., Sendai, Japan
Abstract: Background: The deposition of senile plaques (SPs) and neurofibrillary tangles (NFTs) represents a pathological hallmark of Alzheimer’s disease (AD). Recent advances in the development of PET imaging radiotracers such as [18F]FDDNP, [11C]Pittsburgh Compound-B (PiB), and [11C]BF-227, resulted in successful detection of amyloid deposition in the living human brains. Recently we developed a novel ligand, [18F]THK-523, for in vivo imaging of tau proteins. In this study, we compared the binding properties of THK-523 to synthetic protein fibrils and human brain tissue with amyloid imaging probes such as BF-227 and FDDNP. Methods: In vitro radioligand binding assays were conducted using synthetic Aβ40 and K18ΔK280 tau fibrils. Non-specific binding was determined by the mixture of 2 μM unlabeled compounds. In vitro autoradiography was conducted using AD hippocampal brain sections to examine the radioligand binding to neuropathological lesions. Results: In vitro binding assay indicated that [18F]THK-523 bound to tau fibrils with higher affinity than Aβ40 fibrils, while [18F]BF-227 bound to Aβ40 fibrils with higher affinity than that to tau fibrils. Autoradiographic analysis indicated that [18F]THK-523 accumulated in CA1 region of AD hippocampus, which contains high density of tau deposits. On the other hand, [18F]BF-227 accumulated in the region which contains high density amyloid burden. [18F]FDDNP showed low binding affinity to both Aβ40 and tau fibrils and did not show any significant accumulation in AD hippocampus. Conclusion: This study demonstrated the unique binding property of [18F]THK-523, suggesting the usefulness of this probe for selective identification of tau pathology in AD brain.
Disclosures:  R. Harada: None. N. Okamura: None. S. Furumoto: None. T. Yoshikawa: None. H. Arai: None. Y. Kudo: None. K. Yanai: None.
Keyword(s): Alzheimer's disease
tau imaging
Positron Emission Tomography
[Authors]. [Abstract Title]. Program No. XXX.XX. 2011 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2011. Online.

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