Visualization of Free Radicals by MRI Spin-Trapping Method

通过 MRI 自旋捕获方法可视化自由基

基本信息

批准号：
11670923
负责人：
FUJII Hirotada
金额：
$ 2.37万
依托单位：
Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670923/
关键词：
free radicals non-invasive visualization ESR MRI spin trapping NO T1

项目摘要

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.

体内电子自旋共振 (ESR) 自旋捕获的最终目标是为活体生物体内随时间变化的自由基的表征和定量提供一个窗口。然而，体内 ESR 在涉及活性氧自由基的系统中的实际应用已被证明具有挑战性。其中一些限制与仪器灵敏度有关，特别是与这些自由基的相对稳定性以及剂量毒性限制有关。我们展示了一种新的第一种方法，即所谓的 MRI 自旋捕获方法，可以可视化一氧化氮 (NO) 自由基的分布。 NO与Fe(II)-螯合物自旋陷阱、N-甲基-D-葡萄糖胺二硫代氨基甲酸酯(MGD)络合，通过ESR验证为(MGD)_2-Fe(II)-NO，并通过MRI可视化NO的分布在大鼠中，(MGD)_2-Fe(II)-NO 复合物集中在肝脏中，显示肝静脉和下腔静脉等血管结构的对比度显着增强。通过预先给予竞争性抑制剂，导致 MR 图像的增强减弱，证实一氧化氮合酶是感染性休克大鼠中 NO 的来源。与其他稳定的含氮自由基（例如硝基氧）相比，NO复合物在体内更稳定，并且是更有效的MRI造影剂。当与适当的自旋捕获剂结合使用时，MRI 自旋捕获方法应该是可视化组织中自由基空间分布的有力工具。