A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST)

A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST)
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DOI:
10.1006/jmre.1999.1956
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发表时间:
2000-03-01
影响因子:
2.2
通讯作者:
Balaban, RS
Balaban, RS
中科院分区:
化学3区
文献类型:
--
作者:
Ward, KM;Aletras, AH;Balaban, RS

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先前已经显示,可以使用饱和转移技术根据其水质子汇率来成像内在的代谢产物。这项研究的目的是确定一个适当的化学交换位点,该化学交换位点可以用作外源化学交换依赖性饱和转移(CEST)对比剂在生理条件下,这些药物将通过化学交换来减少水质子信号来起作​​用通过饱和转移在代理上的位置。理想的化学交换地点将与水具有较大的化学转移,这允许高汇率在生理pH(6.5-7.6)和温度(37摄氏度)时接近快速交换限制,并且可以最大程度地减少与磁性相关的问题现场敏感性。在这项初步研究中,评估了许多候选化学物质(氨基酸,糖,核苷酸,杂环化学物质)。其中,在pH,温度和浓度CEST效应方面,巴比妥酸和5,6-二氢酸的表征更加充分。发现的最佳化学交换位点是5-羟色属pophan的5.33-PPM吲哚环-NH位点,这些数据表明,基于CEST的MRI基于CEST的外源性对比剂是可行的。
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.