体内分布
体内
化学
荧光寿命成像显微镜
离解常数
重组DNA
临床前影像学
荧光
分子生物学
生物物理学
生物化学
体外
生物
受体
基因
物理
生物技术
量子力学
作者
Takeshi Fuchigami,Masao Kawasaki,Ryusuke Koyama,Mari Nakaie,Takehiro Nakagaki,Kazunori Sano,Ryuichiro Atarashi,Sakura Yoshida,Mamoru Haratake,Masahiro Ono,Noriyuki Nishida,Morio Nakayama
出处
期刊:ACS Infectious Diseases
[American Chemical Society]
日期:2019-03-15
卷期号:5 (12): 2003-2013
被引量:6
标识
DOI:10.1021/acsinfecdis.8b00184
摘要
Prion diseases are fatal neurodegenerative disorders associated with the deposition of abnormal prion protein aggregates (PrPSc) in the brain tissue. Here, we report the development of 125I-labeled iodobenzofuran (IBF) derivatives as single photon emission computed tomography (SPECT) imaging probes to detect cerebral PrPSc deposits. We synthesized and radioiodinated several 5-IBF and 6-IBF derivatives. The IBF derivatives were evaluated as prion imaging probes using recombinant mouse prion protein (rMoPrP) aggregates and brain sections of mouse-adapted bovine spongiform encephalopathy (mBSE)-infected mice. Although all the IBF derivatives were strongly adsorbed on the rMoPrP aggregates, [125I]5-IBF-NHMe displayed the highest adsorption rate and potent binding affinity with an equilibrium dissociation constant (Kd) of 12.3 nM. Fluorescence imaging using IBF-NHMe showed clear signals of the PrPSc-positive amyloid deposits in the mBSE-infected mouse brains. Biodistribution studies in normal mice demonstrated slow uptake and clearance from the brain of 125I-IBF derivatives. Among the derivatives, [125I]6-IBF-NH2 showed the highest peak brain uptake [2.59% injected dose (ID)/g at 10 min] and good clearance (0.51% ID/g at 180 min). Although the brain distribution of IBF derivatives should still be optimized for in vivo imaging, these compounds showed prospective binding properties to PrPSc. Further chemical modification of these IBF derivatives may contribute to the discovery of clinically applicable prion imaging probes.
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