用于检测肝脏中过量铜(II)的响应性磁共振成像造影剂。
A Responsive Magnetic Resonance Imaging Contrast Agent for Detection of Excess Copper(II) in the Liver .
机构信息
Department of Chemistry and Biochemistry , University of Texas at Dallas , Richardson , Texas , United States.
Advanced Imaging Research Center , University of Texas Southwestern Medical Center , Dallas , Texas , United States.
出版信息
J Am Chem Soc. 2019 Jul 17;141(28):11009-11018. doi: 10.1021/jacs.8b13493. Epub 2019 Jul 3.
The design, synthesis, and properties of a new gadolinium-based copper-responsive magnetic resonance imaging (MRI) contrast agent is presented. The sensor (GdL) has high selectivity for copper ions and exhibits a 43% increase in relaxivity (20 MHz) upon binding to 1 equiv of Cu in aqueous buffer. Interestingly, in the presence of physiological levels of human serum albumin (HSA), the relaxivity is amplified further up to 270%. Additional spectroscopic and X-ray absorption spectroscopy (XAS) studies show that Cu is coordinated by two carboxylic acid groups and the single amine group on an appended side chain of GdL and forms a ternary complex with HSA (GdL-Cu-HSA). -weighted imaging demonstrates that GdL 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.
本文介绍了一种基于钆的新型铜响应磁共振成像（MRI）造影剂的设计、合成及性质。该传感器（GdL）对铜离子具有高选择性，在水缓冲液中与 1 当量的 Cu 结合后，弛豫率（20 MHz）提高了 43%。有趣的是，在生理浓度的人血清白蛋白（HSA）存在下，弛豫率进一步放大至 270%。进一步的光谱和 X 射线吸收光谱（XAS）研究表明，Cu 与 GdL 上附加侧链的两个羧酸基团和单个胺基配位，并与 HSA 形成三元配合物（GdL-Cu-HSA）。T1 加权成像表明，GdL 可检测活鼠体内基础、内源性不稳定的铜（II）离子。这为探索铜离子在威尔逊病等神经退行性疾病的发展和进展中的作用提供了独特的机会。
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