Investigating GluCEST and its specificity for pH mapping at low temperatures
Investigating GluCEST and its specificity for pH mapping at low temperatures
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DOI：
10.1002/nbm.3416
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发表时间：
2015-11-01
影响因子：
2.9
通讯作者：
Dreher, Wolfgang
中科院分区：
文献类型：
--
作者：
Wermter, Felizitas C.;Bock, Christian;Dreher, Wolfgang
谷氨酸-水化学交换饱和转移（CEST）（GluCEST）是研究谷氨酸浓度和细胞内pH的有力工具，也有助于了解低等水生脊椎动物和无脊椎动物的生理。因此，本研究旨在研究GluCEST效应和在宽温度范围（1-37 ℃）和pH值（5.5-8.0）内谷氨酸盐的胺质子与水的交换速率k（sw）。在不同的pH值和温度下从谷氨酸盐溶液中测量Z-光谱，并通过数值求解Bloch-McConnell方程进行分析。正如预期的那样，观察到GluCEST效应和测定的k（sw）值对pH和温度的强烈依赖性。此外，证实了GluCEST效应对磷酸盐缓冲液浓度的强烈依赖性。体外数据表明，GluCEST在整个温度范围内都是可检测的，甚至在1摄氏度。对于所考虑的温度和pH值范围，确定了交换率k（sw）的插值函数，显示了在给定温度下交换率和pH之间的双射关系。为了研究低温下GluCEST成像的特异性，研究了与脑CEST成像相关的几种代谢物的CEST效应。作为一个例子，在3 ppm的GluCEST的总CEST效应的贡献估计为斑马鱼（Danio rerio）。它表明，在较低的温度下，谷氨酸是总CEST效应的主要贡献者，特别是如果实验参数进行了优化。版权所有（c）2015约翰威利父子有限公司
Chemical exchange saturation transfer (CEST) from glutamate to water (GluCEST) is a powerful tool for mapping glutamate concentration and intracellular pH. GluCEST could also be helpful to understand the physiology of lower aquatic vertebrates and invertebrates. Therefore, this study aimed to investigate the GluCEST effect and the exchange rate k(sw) from amine protons of glutamate to water in a broad range of temperatures (1-37 degrees C) and pH (5.5-8.0). Z-spectra were measured from glutamate solutions at different pH values and temperatures and analysed by numerically solving the Bloch-McConnell equation. As expected, a strong dependence of the GluCEST effect and the determined k(sw) values on pH and temperature was observed. In addition, a strong dependence of the GluCEST effect on phosphate buffer concentration was confirmed. The in vitro data show that GluCEST is detectable in the whole temperature range, even at 1 degrees C. An interpolation function for the exchange rate k(sw) was determined for the considered range of temperatures and pH values, showing a bijective relation between the exchange rate and pH at a given temperature. To investigate the specificity of GluCEST imaging at low temperatures, the CEST effect was investigated for several metabolites relevant for CEST imaging of the brain. As an example, the contribution of GluCEST to the total CEST effect at 3ppm was estimated for zebrafish (Danio rerio). It is shown that also at lower temperatures glutamate is the major contributor to the total CEST effect, particularly if the experimental parameters are optimized. Copyright (c) 2015 John Wiley & Sons, Ltd.