Advanced Magnetic Resonance Center , Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
Antioxid Redox Signal. 2018 May 20;28(15):1404-1415. doi: 10.1089/ars.2017.7390. Epub 2017 Dec 11.
In vivo free radical imaging in preclinical models of disease has become a reality. Free radicals have traditionally been characterized by electron spin resonance (ESR) or electron paramagnetic resonance (EPR) spectroscopy coupled with spin trapping. The disadvantage of the ESR/EPR approach is that spin adducts are short-lived due to biological reductive and/or oxidative processes. Immuno-spin trapping (IST) involves the use of an antibody that recognizes macromolecular 5,5-dimethyl-pyrroline-N-oxide (DMPO) spin adducts (anti-DMPO antibody), regardless of the oxidative/reductive state of trapped radical adducts. Recent Advances: The IST approach has been extended to an in vivo application that combines IST with molecular magnetic resonance imaging (mMRI). This combined IST-mMRI approach involves the use of a spin-trapping agent, DMPO, to trap free radicals in disease models, and administration of an mMRI probe, an anti-DMPO probe, which combines an antibody against DMPO-radical adducts and an MRI contrast agent, resulting in targeted free radical adduct detection.
The combined IST-mMRI approach has been used in several rodent disease models, including diabetes, amyotrophic lateral sclerosis (ALS), gliomas, and septic encephalopathy. The advantage of this approach is that heterogeneous levels of trapped free radicals can be detected directly in vivo and in situ to pin point where free radicals are formed in different tissues.
The approach can also be used to assess therapeutic agents that are either free radical scavengers or generate free radicals. Smaller probe constructs and radical identification approaches are being considered. The focus of this review is on the different applications that have been studied, advantages and limitations, and future directions. Antioxid. Redox Signal. 28, 1404-1415.
在疾病的临床前模型中，体内自由基成像是一种现实。自由基传统上通过电子自旋共振（ESR）或电子顺磁共振（EPR）光谱与自旋捕获相结合来表征。ESR/EPR 方法的缺点是由于生物还原和/或氧化过程，自旋加合物的寿命很短。免疫自旋捕获（IST）涉及使用识别大分子 5,5-二甲基-吡咯啉-N-氧化物（DMPO）自旋加合物（抗-DMPO 抗体）的抗体，而不管捕获的自由基加合物的氧化/还原状态如何。最新进展：IST 方法已扩展到一种体内应用，该应用将 IST 与分子磁共振成像（mmRI）结合使用。这种联合的 IST-mmRI 方法涉及使用自旋捕获剂 DMPO 在疾病模型中捕获自由基，并施用 mMRI 探针，即抗-DMPO 探针，该探针结合了针对 DMPO-自由基加合物的抗体和 MRI 造影剂，导致靶向自由基加合物的检测。
联合的 IST-mmRI 方法已在几种啮齿动物疾病模型中使用，包括糖尿病、肌萎缩侧索硬化症（ALS）、神经胶质瘤和脓毒性脑病。这种方法的优点是可以直接在体内和原位检测到捕获的自由基的异质水平，以确定不同组织中自由基的形成位置。
该方法还可用于评估既是自由基清除剂又是自由基生成剂的治疗剂。正在考虑更小的探针结构和自由基识别方法。本综述的重点是研究了不同的应用，包括优势和局限性以及未来的方向。抗氧化。氧化还原信号。28，1404-1415。
