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タイトル: Characterisation of radioiodinated flavonoid derivatives for SPECT imaging of cerebral prion deposits
著者: Fuchigami, Takeshi
Yamashita, Yuki
Kawasaki, Masao
Ogawa, Ayaka
Haratake, Mamoru
Atarashi, Ryuichiro
Sano, Kazunori
Nakagaki, Takehiro
Ubagai, Kaori
Ono, Masahiro  kyouindb  KAKEN_id
Yoshida, Sakura
Nishida, Noriyuki
Nakayama, Morio
著者名の別形: 小野, 正博
発行日: 16-Dec-2015
出版者: Nature Publishing Group
誌名: Scientific Reports
巻: 5
論文番号: 18440
抄録: Prion diseases are fatal neurodegenerative diseases characterised by deposition of amyloid plaques containing abnormal prion protein aggregates (PrPSc). This study aimed to evaluate the potential of radioiodinated flavonoid derivatives for single photon emission computed tomography (SPECT) imaging of PrPSc. In vitro binding assays using recombinant mouse PrP (rMoPrP) aggregates revealed that the 4-dimethylamino-substituted styrylchromone derivative (SC-NMe2) had higher in vitro binding affinity (Kd = 24.5 nM) and capacity (Bmax = 36.3 pmol/nmol protein) than three other flavonoid derivatives (flavone, chalcone, and aurone). Fluorescent imaging using brain sections from mouse-adapted bovine spongiform encephalopathy (mBSE)-infected mice demonstrated that SC-NMe2 clearly labelled PrPSc-positive prion deposits in the mice brain. Two methoxy SC derivatives, SC-OMe and SC-(OMe)2, also showed high binding affinity for rMoPrP aggregates with Ki values of 20.8 and 26.6 nM, respectively. In vitro fluorescence and autoradiography experiments demonstrated high accumulation of [125I]SC-OMe and [125I]SC-(OMe)2 in prion deposit-rich regions of the mBSE-infected mouse brain. SPECT/computed tomography (CT) imaging and ex vivo autoradiography demonstrated that [123I]SC-OMe showed consistent brain distribution with the presence of PrPSc deposits in the mBSE-infected mice brain. In conclusion, [123I]SC-OMe appears a promising SPECT radioligand for monitoring prion deposit levels in the living brain.
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/2433/215978
DOI(出版社版): 10.1038/srep18440
PubMed ID: 26669576
出現コレクション:学術雑誌掲載論文等

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