A self-calibrating PARACEST MRI contrast agent that detects esterase enzyme activity.
A self-calibrating PARACEST MRI contrast agent that detects esterase enzyme activity.
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DOI：
10.1002/cmmi.421
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发表时间：
2011-07
影响因子：
--
通讯作者：
Pagel MD
中科院分区：
文献类型：
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作者：
Li Y;Sheth VR;Liu G;Pagel MD
许多PARACEST MRI造影剂的CEST效应随分子生物标志物的变化而变化。然而，其他分子生物标志物或环境因素可以影响CEST，使得CEST的变化不是检测生物标志物的决定性证据。为了克服这个问题，第二对照CEST效应可以包括在相同的PARACEST试剂中，其响应于除了待测量的生物标志物之外的改变第一CEST效应的所有因素。为了研究这种方法，开发了一种PARACEST MRI造影剂，其中一种CEST效应对酯酶活性有反应，另一种CEST效应对酯酶活性有反应。两种CEST效应的比率与浓度和T1弛豫无关，因此该试剂相对于这些因素是自校准的。该比率法依赖于温度，并且受MR聚结的影响，因为随着温度的升高，化学交换速率接近可交换质子的化学位移。两种CEST效应还显示了具有不同pH依赖性的证据，因此该试剂不能相对于pH进行自校准。因此，自校准PARACEST MRI造影剂可以更准确地检测分子生物标志物，例如酯酶活性，只要温度和pH在可接受的生理范围内并保持恒定。
The CEST effect of many PARACEST MRI contrast agents changes in response to a molecular biomarker. However, other molecular biomarkers or environmental factors can influence CEST, so that a change in CEST is not conclusive proof for detecting the biomarker. To overcome this problem, a second control CEST effect may be included in the same PARACEST agent, which is responsive to all factors that alter the first CEST effect except for the biomarker to be measured. To investigate this approach, a PARACEST MRI contrast agent was developed with one CEST effect that is responsive to esterase enzyme activity and a second control CEST effect. The ratio of the two CEST effects was independent of concentration and T1 relaxation, so that this agent was self-calibrating with respect to these factors. This ratiometric method was dependent on temperature and was influenced by MR coalescence as the chemical exchange rates approached the chemical shifts of the exchangable protons as temperature was increased. The two CEST effects also showed evidence of having different pH dependencies, so that this agent was not self-calibrating with respect to pH. Therefore, a self-calibrating PARACEST MRI contrast agent can more accurately detect a molecular biomarker such as esterase enzyme activity, as long as temperature and pH are within an acceptable physiological range and remain constant.