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タイトル: Highly Selective Tau-SPECT Imaging Probes for Detection of Neurofibrillary Tangles in Alzheimer’s Disease
著者: Ono, Masahiro  kyouindb  KAKEN_id
Watanabe, Hiroyuki  kyouindb  KAKEN_id
Kitada, Ayane
Matsumura, Kenji
Ihara, Masafumi
Saji, Hideo
著者名の別形: 小野, 正博
渡邊, 裕之
北田, 彩音
松村, 憲志
猪原, 匡史
佐治, 英郎
発行日: Dec-2016
出版者: Springer Nature
誌名: Scientific Reports
巻: 6
論文番号: 34197
抄録: Neurofibrillary tangles composed of aggregates of hyperphosphorylated tau proteins are one of the neuropathological hallmarks of Alzheimer’s disease (AD) in addition to the deposition of β-amyloid plaques. Since the deposition of tau aggregates is closely associated with the severity of AD, the in vivo detection of tau aggregates may be useful as a biomarker for the diagnosis and progression of AD. In this study, we designed and synthesized a new series of radioiodinated benzoimidazopyridine (BIP) derivatives, and evaluated their utility as single photon emission computed tomography (SPECT) imaging agents targeting tau aggregates in AD brains. Five radioiodinated BIP derivatives were successfully prepared in high radiochemical yields and purities. In in vitro autoradiographic studies using postmortem AD brains, all BIP derivatives displayed high accumulation of radioactivity in the brain sections with abundant neurofibrillary tangles, while no marked radioactivity accumulation was observed in the brain sections with only β-amyloid aggregates, indicating that the BIP derivatives exhibited selective binding to tau aggregates. Biodistribution studies in normal mice showed high brain uptake at 2 min postinjection (3.5–4.7% ID/g) and rapid clearance at 60 min postinjection (0.04–0.23% ID/g), which is highly desirable for tau imaging agents. The results of the present study suggest that [123I]BIP derivatives may be useful SPECT agents for the in vivo imaging of tau aggregates in AD.
著作権等: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
URI: http://hdl.handle.net/2433/218821
DOI(出版社版): 10.1038/srep34197
出現コレクション:学術雑誌掲載論文等

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