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論文
- タイトル
- タイトル(英)
- Synthesis and Evaluation of 18F-Labeled Chalcone Analogue for Detection of α-Synuclein Aggregates in the Brain Using the Mouse Model.
- 参照URL
- https://researchmap.jp/masatohasegawa/published_papers/40778609
- 著者
- 著者(英)
- Sho Kaide,Hiroyuki Watanabe,Shimpei Iikuni,Masato Hasegawa,Masahiro Ono
- 担当区分
- 概要
- 概要(英)
- In the brains of patients with synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, α-synuclein (α-syn) aggregates deposit abnormally to induce neurodegeneration, although the mechanism is unclear. Thus, in vivo imaging studies targeting α-syn aggregates have attracted much attention to guide medical intervention against synucleinopathy. In our previous study, a chalcone analogue, [125I]PHNP-3, functioned as a feasible probe in terms of α-syn binding in vitro; however, it did not migrate to the mouse brain, and further improvement of brain uptake was required. In the present study, we designed and synthesized two novel 18F-labeled chalcone analogues, [18F]FHCL-1 and [18F]FHCL-2, using a central nervous system multiparameter optimization (CNS MPO) algorithm with the aim of improving blood-brain barrier permeation in the mouse brain. Then, we evaluated their utility for in vivo imaging of α-syn aggregates using a mouse model. In the competitive inhibition assay, both chalcone analogues exhibited high binding affinity for α-syn aggregates (Ki = 2.6 and 3.4 nM, respectively), while no marked amyloid β (Aβ)-binding was observed. The 18F-labeling reaction was successfully performed. In a biodistribution experiment, brain uptake of both chalcone analogues in normal mice (2.09 and 2.40% injected dose/gram (% ID/g) at 2 min postinjection, respectively) was higher than that of [125I]PHNP-3, suggesting that the introduction of 18F into the chalcone analogue led to an improvement in brain uptake in mice while maintaining favorable binding ability for α-syn aggregates. Furthermore, in an ex vivo autoradiography experiment, [18F]FHCL-2 showed the feasibility of the detection of α-syn aggregates in the mouse brain in vivo. These preclinical studies demonstrated the validity of the design of α-syn-targeting probes based on the CNS MPO score and the possibility of in vivo imaging of α-syn aggregates in a mouse model using 18F-labeled chalcone analogues.
- 出版者・発行元
- 出版者・発行元(英)
- 誌名
- 誌名(英)
- ACS chemical neuroscience
- 巻
- 13
- 号
- 20
- 開始ページ
- 2982
- 終了ページ
- 2990
- 出版年月
- 2022年10月19日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文(学術雑誌)
- ISSN
- DOI URL
- https://doi.org/10.1021/acschemneuro.2c00473
- 共同研究・競争的資金等の研究課題
研究者
Hasegawa Masato
( )