A Responsive Magnetic Resonance Imaging Contrast Agent for Detection of Excess Copper(II) in the Liver In Vivo.
A Responsive Magnetic Resonance Imaging Contrast Agent for Detection of Excess Copper(II) in the Liver In Vivo.
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DOI：
10.1021/jacs.8b13493
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发表时间：
2019-06
影响因子：
15
通讯作者：
Namini N Paranawithana;A. Martins;Veronica Clavijo Jordan;P. Zhao;S. Chirayil;Gabriele Meloni;A. Sherry
中科院分区：
文献类型：
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作者：
Namini N Paranawithana;A. Martins;Veronica Clavijo Jordan;P. Zhao;S. Chirayil;Gabriele Meloni;A. Sherry
本文介绍了一种新型的格拉基铜响应磁共振成像(MRI)造影剂的设计、合成和性能。该传感器(GdL1)对铜离子具有很高的选择性，在水溶液中与1当量的Cu2+结合时，R1驰豫率(20 MHz)增加了43%。有趣的是，在生理水平的人血清白蛋白(HSA)存在的情况下，R1的松弛系数进一步放大到270%。另外的光谱和X射线吸收光谱(XAS)研究表明，Cu2+与GdL1侧链上的两个羧酸基和单胺基配位，并与HSA形成三元络合物(GdL1-Cu2+-HSA)。T1加权体内成像表明，GdL1可以在活着的小鼠体内检测到基础的、内源性的不稳定铜(II)离子。这为探索铜离子在威尔逊病等神经系统疾病的发生和发展中的作用提供了一个独特的机会。
The design, synthesis, and properties of a new gadolinium-based copper-responsive magnetic resonance imaging (MRI) contrast agent is presented. The sensor (GdL1) has high selectivity for copper ions and exhibits a 43% increase in r1 relaxivity (20 MHz) upon binding to 1 equiv of Cu2+ in aqueous buffer. Interestingly, in the presence of physiological levels of human serum albumin (HSA), the r1 relaxivity is amplified further up to 270%. Additional spectroscopic and X-ray absorption spectroscopy (XAS) studies show that Cu2+ is coordinated by two carboxylic acid groups and the single amine group on an appended side chain of GdL1 and forms a ternary complex with HSA (GdL1-Cu2+-HSA). T1-weighted in vivo imaging demonstrates that GdL1 can detect basal, endogenous labile copper(II) ions in living mice. This offers a unique opportunity to explore the role of copper ions in the development and progression of neurological diseases such as Wilson's disease.