Ward K M, Aletras A H, Balaban R S
Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Bethesda, Maryland 20892-1061, USA.
J Magn Reson. 2000 Mar;143(1):79-87. doi: 10.1006/jmre.1999.1956.
It has been previously shown that intrinsic metabolites can be imaged based on their water proton exchange rates using saturation transfer techniques. The goal of this study was to identify an appropriate chemical exchange site that could be developed for use as an exogenous chemical exchange dependent saturation transfer (CEST) contrast agent under physiological conditions. These agents would function by reducing the water proton signal through a chemical exchange site on the agent via saturation transfer. The ideal chemical exchange site would have a large chemical shift from water. This permits a high exchange rate without approaching the fast exchange limit at physiological pH (6.5-7.6) and temperature (37 degrees C), as well as minimizing problems associated with magnetic field susceptibility. Numerous candidate chemicals (amino acids, sugars, nucleotides, heterocyclic ring chemicals) were evaluated in this preliminary study. Of these, barbituric acid and 5, 6-dihydrouracil were more fully characterized with regard to pH, temperature, and concentration CEST effects. The best chemical exchange site found was the 5.33-ppm indole ring -NH site of 5-hydroxytryptophan. These data demonstrate that a CEST-based exogenous contrast agent for MRI is feasible.
先前的研究表明，利用饱和转移技术，基于内源性代谢物的水质子交换速率可以对其进行成像。本研究的目的是确定一个合适的化学交换位点，该位点可在生理条件下开发用作外源性化学交换依赖饱和转移（CEST）造影剂。这些造影剂的作用机制是通过饱和转移，经由造影剂上的一个化学交换位点来降低水质子信号。理想的化学交换位点与水的化学位移应较大。这允许在生理pH值（6.5 - 7.6）和温度（37摄氏度）下有较高的交换速率，而不接近快速交换极限，同时还能将与磁场敏感性相关的问题降至最低。在这项初步研究中，对众多候选化学物质（氨基酸、糖类、核苷酸、杂环化学物质）进行了评估。其中，巴比妥酸和5,6 - 二氢尿嘧啶在pH值、温度和浓度对CEST的影响方面得到了更全面的表征。所发现的最佳化学交换位点是5 - 羟色氨酸的5.33 ppm吲哚环 -NH位点。这些数据表明，基于CEST的MRI外源性造影剂是可行的。
