Comparison of the binding characteristics of [¹⁸F]SNFT-1 and other tau imaging tracers to Alzheimer's disease pathology
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- Yuka Yokoyama
- Department of Pharmacology, Tohoku University Graduate School of Medicine
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- Harada Ryuichi
- Department of Pharmacology, Tohoku University Graduate School of Medicine
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- Pradith Lerdsirisuk
- Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University
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- Shimizu Yuki
- Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University
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- Du Yiqing
- Department of Pharmacology, Tohoku University Graduate School of Medicine
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- Ishikawa Yoichi
- Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University
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- Arai Hiroyuki
- Cyclotron and Radioisotope Center, Tohoku University
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- Kudo Yukitsuka
- Cyclotron and Radioisotope Center, Tohoku University
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- Furumoto Syozo
- Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University
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- Okamura Nobuyuki
- Divison of Pharmacology, Tohoku Medical and Pharmaceutical University
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- Yanai Kazuhiko
- Department of Pharmacology, Tohoku University Graduate School of Medicine
Bibliographic Information
- Other Title
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- 第二世代タウPETトレーサーの結合性比較
Abstract
<p>Introduction: Misfolded tau aggregates associated with clinical syndromes and various neurodegenerative diseases. To date, many second-generation of tau PET tracers were developed to overcome the limitation of the first-generation such as off-target binding. Recently, we developed [¹⁸F]SNFT-1 from compound optimization of [¹⁸F]THK-5351, which showed high affinity for monoamine oxidase-B (MAO-B) as off-target binding. The aim of study was to compare the binding properties of [¹⁸F]SNFT-1 and second-generation tau PET radiotracers to human brain tissues.</p><p>Methods: In vitro competitive binding assay were performed for tau aggregates, amyloid aggregates, and recombinant MAO-A and MAO-B. After preparing 18F-labeled compounds, in vitro autoradiography was performed using frozen human brain sections with immunostaining of phosphorylated tau (tau IHC) for evaluation of binding selectivity.</p><p>Results and Discussion: Although second-generation of tau PET radiotracers showed a similar binding affinity for tau aggregates, the off-target binding affinity was different. SNFT-1 showed a high binding affinity for tau aggregates, which was comparable to MK-6240, with no interaction of amyloid aggregates as well as MAO enzymes. In vitro autoradiography demonstrated that distribution of radiotracer's binding was similar to tau IHC in the medial temporal area of Alzheimer's disease. On the other hands, second-generation tau PET radiotracers showed little binding to the frontal cortex in a case of progressive supranuclear palsy that contains high density tau aggregates. </p><p>Conclusion: [18F]SNFT-1 would be a promising candidates for imaging tau aggregates. Further binding characterization is required to validate the binding of non-AD tau aggregates.</p>
Journal
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- Proceedings for Annual Meeting of The Japanese Pharmacological Society
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Proceedings for Annual Meeting of The Japanese Pharmacological Society 95 (0), 1-SS-45-, 2022
Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390573242665295360
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- ISSN
- 24354953
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- Text Lang
- ja
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- Data Source
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- JaLC
- Crossref
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- Abstract License Flag
- Disallowed