当前位置: X-MOL 学术ACS Chem. Neurosci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Design, Synthesis, and Preliminary Evaluation of SPECT Probes for Imaging β-Amyloid in Alzheimer’s Disease Affected Brain
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2018-03-27 00:00:00 , DOI: 10.1021/acschemneuro.8b00064
Yuki Okumura 1, 2 , Yoshifumi Maya 1 , Takako Onishi 1 , Yoshinari Shoyama 1 , Akihiro Izawa 1 , Daisaku Nakamura 1 , Shigeyuki Tanifuji 1 , Akihiro Tanaka 1 , Yasushi Arano 2 , Hiroki Matsumoto 1
Affiliation  

In this study, we synthesized of a series of 2-phenyl- and 2-pyridyl-imidazo[1,2-a]pyridine derivatives and examine their suitability as novel probes for single-photon emission computed tomography (SPECT)-based imaging of β-amyloid (Aβ). Among the 11 evaluated compounds, 10 showed moderate affinity to Aβ(1–42) aggregates, exhibiting half-maximal inhibitory concentrations (IC50) of 14.7 ± 6.07–87.6 ± 39.8 nM. In vitro autoradiography indicated that 123I-labeled triazole-substituted derivatives displayed highly selective binding to Aβ plaques in the hippocampal region of Alzheimer’s disease (AD)-affected brain. Moreover, biodistribution studies performed on normal rats demonstrated that all 123I-labeled probes featured high initial uptake into the brain followed by a rapid washout and were thus well suited for imaging Aβ plaques, with the highest selectivity observed for a 1H-1,2,3-triazole-substituted 2-pyridyl-imidazopyridine derivative, [123I]ABC577. This compound showed good kinetics in rat brain as well as moderate in vivo stability in rats and is thus a promising SPECT imaging probe for AD in clinical settings.

中文翻译:

SPECT探针的设计,合成和初步评估,以对受阿尔茨海默氏病影响的大脑中的β-淀粉样蛋白进行成像

在这项研究中,我们合成了一系列的2-苯基-和2-吡啶基-咪唑并[1,2- a ]吡啶衍生物,并检验了它们作为基于单光子发射计算机断层摄影(SPECT)成像的新型探针的适用性。 β-淀粉样蛋白(Aβ)。在11种被评估的化合物中,有10种对Aβ(1-42)聚集体表现出中等亲和力,半数抑制浓度(IC 50)为14.7±6.07-87.6±39.8 nM。体外放射自显影表明,123 I标记的三唑取代的衍生物对受阿尔茨海默氏病(AD)影响的海马区的Aβ斑块表现出高度选择性的结合。此外,对正常大鼠进行的生物分布研究表明,所有123I标记的探针具有很高的初始摄入量,随后被快速洗去,因此非常适合于对Aβ斑进行成像,对1 H -1,2,3-三唑取代的2-吡啶基-咪唑并吡啶具有最高的选择性导数,[ 123 I] ABC577。该化合物在大鼠脑中显示出良好的动力学以及在大鼠中具有适度的体内稳定性,因此是临床上用于AD的有前途的SPECT成像探针。
更新日期:2018-03-27
down
wechat
bug