Feasibility and assessment of non-invasive in vivo redox status using electron paramagnetic resonance imaging.
Feasibility and assessment of non-invasive in vivo redox status using electron paramagnetic resonance imaging.
复制标题
使用电子顺磁共振成像非侵入性体内氧化还原状态的可行性和评估。
DOI：
10.1080/j.1600-0455.2002.430418.x
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Krishna,MC
中科院分区：
文献类型：
--
作者：
Yamada,K-I;Kuppusamy,P;English,S;Yoo,J;Irie,A;Subramanian,S;Mitchell,JB;Krishna,MC
目的：测试电子顺磁共振成像（EPRI）使用氧化还原敏感顺磁造影剂提供组织氧化还原状态非侵入性图像的可行性。材料和方法：使用氮氧自由基作为顺磁剂，并将定制的300 MHz EPR光谱仪/成像仪用于所有研究。构建了一个由四个含有等浓度氮氧化合物的试管组成的体模。将不同浓度的次黄嘌呤/黄嘌呤氧化酶加入到每个试管中，并通过EPR监测作为时间函数的氮氧化物的还原。荷瘤小鼠静脉输注氮氧自由基，并使用荷瘤腿和作为对照的正常腿的2D EPR在逐像素的基础上监测相应的减少速率。对于动物研究，静脉内注射氮氧自由基（1.25 mmol/kg），注射后每3分钟使用2.5 G/cm的磁场梯度收集EPR投影。计算逐像素基础上的信号强度的降低速率并绘制为氧化还原图。还从用马来酸二乙酯（DEM）处理的小鼠中收集氧化还原图谱，所述DEM消耗组织硫醇并改变整体氧化还原状态。结果如下：从幻影中获得的氧化还原图谱与每个管中的强度变化一致，其中信号作为酶活性的函数而降低，验证了EPRI准确获得氮氧化物还原变化的能力。EPR的氧化还原成像能力随后在体内进行评价。荷瘤小鼠腿的氮氧分布和还原率的EPR图像比正常组织表现出更大的异质性。还原率被认为是显着降低，在肿瘤的DEM治疗，一致的硫醇耗尽和随之而来的氧化还原状态的改变的小鼠。结论：使用氧化还原敏感的顺磁性造影剂，EPRI可以非侵入性地区分正常组织和肿瘤之间的氧化还原状态差异。
Purpose: To test the feasibility of electron paramagnetic resonance imaging (EPRI) to provide non-invasive images of tissue redox status using redox-sensitive paramagnetic contrast agents. Material and Methods: Nitroxide free radicals were used as paramagnetic agents and a custom-built 300 MHz EPR spectrometer/imager was used for all studies. A phantom was constructed consisting of four tubes containing equal concentrations of a nitroxide. Varying concentrations of hypoxanthine/xanthine oxidase were added to each tube and reduction of the nitroxide was monitored by EPR as a function of time. Tumor-bearing mice were intravenously infused with a nitroxide and the corresponding reduction rate was monitored on a pixel-by-pixel basis using 2D EPR of the tumor-bearing leg and normal leg serving as control. For animal studies, nitroxides were injected intravenously (1.25 mmol/kg) and EPR projections were collected every 3 min after injection using a magnetic field gradient of 2.5 G/cm. The reduction rates of signal intensity on a pixel-by-pixel basis were calculated and plotted as a redox map. Redox maps were also collected from the mice treated with diethylmaleate (DEM), which depletes tissue thiols and alters the global redox status. Results: Redox maps obtained from the phantoms were in agreement with the intensity change in each of the tubes where the signals were decreasing as a function of the enzymatic activity, validating the ability of EPRI to accurately access changes in nitroxide reduction. Redox imaging capability of EPR was next evaluatedin vivo. EPR images of the nitroxide distribution and reduction rates in tumor-bearing leg of mice exhibited more heterogeneity than in the normal tissue. Reduction rates were found to be significantly decreased in tumors of mice treated with DEM, consistent with the depletion of thiols and the consequent alteration of the redox status. Conclusion: Using redox-sensitive paramagnetic contrast agents, EPRI can non-invasively discriminate redox status differences between normal tissue and tumors.
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DOI：
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发表时间：
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期刊：
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