Detecting acid phosphatase enzymatic activity with phenol as a chemical exchange saturation transfer magnetic resonance imaging contrast agent (PhenolCEST MRI).
Detecting acid phosphatase enzymatic activity with phenol as a chemical exchange saturation transfer magnetic resonance imaging contrast agent (PhenolCEST MRI).
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苯酚作为化学交换饱和转移磁共振成像造影剂(PhenolCEST MRI)检测酸性磷酸酶活性。
DOI：
10.1016/j.bios.2019.111442
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发表时间：
2019-09
影响因子：
12.6
通讯作者：
Jia Zhang;Yue Yuan;Zheng Han;Yuguo Li;P. V. van Zijl;Xing Yang;J. Bulte;Guanshu Liu
中科院分区：
文献类型：
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作者：
Jia Zhang;Yue Yuan;Zheng Han;Yuguo Li;P. V. van Zijl;Xing Yang;J. Bulte;Guanshu Liu
苯酚含有一个可交换的羟基质子，在1H核磁共振（1H NMR）光谱中与水的共振频率在4.8 ppm处共振，使其能够在亚mM浓度下通过化学交换饱和转移磁共振成像（CEST MRI）或基于交换的T2弛豫增强（T2ex）效应分别在酸性和碱性条件下检测到。我们最近研究了苯酚及其衍生物的T2ex效应，但苯酚的CEST特性尚不清楚，也没有研究使用苯酚的天然CEST MRI效应来检测酶活性。在此，基于苯酚固有的CEST MR特性，即phenolCEST，我们开发了第一个MRI方法来检测酸性磷酸酶（AcP）酶活性。在pH = 5.0时AcP的活性，非CEST可检测的酶底物磷酸苯酯转化为CEST可检测的苯酚，提供了一种简单的方法来直接定量AcP活性，而不需要第二个信号探针。我们展示了这种phenolCEST生物传感器用于测量前列腺细胞的酶溶液和细胞裂解物中的AcP活性的应用。本工作为酚CEST MRI技术在传感器设计和开发中的应用打开了一扇大门。
Phenol contains an exchangeable hydroxyl proton resonant at 4.8 ppm from the resonance frequency of water in the1H nuclear magnetic resonance (1H NMR) spectrum, enabling itself to be detected at sub-mM concentration by either chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) or exchange-based T2relaxation enhancement (T2ex) effect under acidic and basic conditions, respectively. We recently investigated the T2exeffects of phenol and its derivatives, but the CEST characteristics of phenols are unknown in detail, and no study on using the natural CEST MRI effects of phenol for detecting enzymatic activity has been conducted. Herein, on the basis of the inherent CEST MR property of phenol, namely phenolCEST, we developed the first MRI approach to detect acid phosphatase (AcP) enzymatic activity. Upon the activity of AcP at pH = 5.0, non-CEST-detectable enzyme substrate phenyl phosphate was converted to CEST-detectable phenol, providing a simple way to quantify AcP activity directly without the need for a second signalling probe. We showed the application of this phenolCEST biosensor for measuring AcP activity in both enzyme solutions and cell lysates of prostate cells. This work opens a door for the utilization of phenolCEST MRI technique in sensor design and development.