文章基本信息

标题：Characterisation of radioiodinated flavonoid derivatives for SPECT imaging of cerebral prion deposits
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作者：Takeshi Fuchigami ; Yuki Yamashita ; Masao Kawasaki 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：5
期号：1
DOI：10.1038/srep18440
语种：English
出版社：Springer Nature
摘要：Prion diseases are fatal neurodegenerative diseases characterised by deposition of amyloid plaques containing abnormal prion protein aggregates (PrP^Sc). This study aimed to evaluate the potential of radioiodinated flavonoid derivatives for single photon emission computed tomography (SPECT) imaging of PrP^Sc. 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 ( K _d = 24.5 nM) and capacity ( B _max = 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 PrP^Sc-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 K _i 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 PrP^Sc 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.