Visualization of Free Radicals by MRI Spin-Trapping Method

体内电子自旋共振（ESR）自旋捕获的最终目标是提供一个窗口，以表征和定量的自由基随时间在活的有机体。然而，体内ESR的实际应用涉及活性氧自由基的系统已被证明具有挑战性。这些限制中的一些涉及仪器灵敏度，特别是这些自由基的相对稳定性，以及剂量的毒性限制。我们已经证明了一种新的和第一种方法，所谓的MRI自旋捕获方法，可视化一氧化氮（NO）自由基的分布。用N-甲基-D-葡糖胺二硫代氨基甲酸盐（MGD）与NO形成（MGD）_2-Fe（II）-NO络合物，用MRI观察NO在大鼠肝脏中的分布，发现（MGD）_2-Fe（II）-NO络合物在肝静脉、下腔静脉等血管结构中明显增强。通过预先给予竞争性抑制剂，证实一氧化氮合酶是感染性休克大鼠NO的来源，导致MR图像增强降低。NO复合物在体内更稳定，是一种比其他稳定的含氮自由基（如氮氧自由基）更有效的MRI造影剂。MRI自旋捕获技术与合适的自旋捕获剂相结合，将是一种有效的研究自由基在组织中空间分布的工具。

The ultimate goal of in vivo electron spin resonance (ESR) spin trapping is to provide a window to the characterization and quantification of free radicals with time within living organisms. However, the practical application of in vivo ESR to systems involving reactive oxygen free radicals has proven challenging. Some of these limitations relate to instrument sensitivity and particularly to the relative stability of these radicals, as well as toxicity limitations with dosing. We have demonstrated a new and first approach, so called MRI spin trapping method, to visualize the distribution of nitric oxide (NO) free radicals. NO was complexed with Fe (II)-chelate spin trap, N-methyl-D-glucamine dithiocarbamate (MGD), verified as (MGD)_2-Fe(II)-NO by ESR, and the distribution of NO was visualized by MRI.In rats, (MGD)_2-Fe(II)-NO complex was concentrated in the liver displaying significantly enhanced contrast in the vascular structure such as hepatic vein and inferior vena cava. Nitric oxide synthase was verified as the source of NO in rats with septic shock by pre-administration of the competitive inhibitor, resulting in reduced enhancement of the MR images. The NO complex was more stable in vivo and a more effective MRI contrast agent than other stable nitrogen containing radicals, such as nitroxides. MRI spin trapping method should be a powerful tool for visualizing spatial distribution of free radicals in tissues when combined with the appropriate spin-trapping agents.