Abstract
In vivo free radical imaging in pre-clinical models of disease is now possible. Free radicals have traditionally been characterized by ESR or EPR spin trapping spectroscopy. 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 DMPO-spin adducts (anti-DMPO antibody), regardless of the oxidative/reductive state of trapped radical adducts. 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 a mMRI probe, an anti-DMPO probe, that combines an antibody against DMPO-radical adducts and a 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, 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. The focus of this review will be on the different applications that have been studied, advantages and limitations, and future directions.
Highlights
It is well known that free radicals play a role in the pathogenesis associated with various diseases such as diabetes, septic encephalopathy, neurodegenerative diseases, and cancers, to mention a few
Chronic oxidative stress and inflammation, both associated with obesity, can lead to insulin resistance, dysregulated metabolic pathways, diabetes and cardiovascular diseases, via impaired signaling and metabolism that result in insulin secretion dysfunction, insulin action, and immune responses [1]
For over half a century, free radicals were characterized by electron spin resonance (ESR) or electron paramagnetic resonance (EPR) spectroscopy coupled with spin trapping
Summary
Reactive oxygen and nitrogen species (RONS) lead to structural and functional modifications of cellular proteins and lipids, resulting in cellular dysfunction, such as impaired energy metabolism, altered cell signaling and cell cycle control, impaired cell transport processes and dysfunctional biological activities, immune activation, and inflammation [1]. Chronic oxidative stress and inflammation, both associated with obesity, can lead to insulin resistance, dysregulated metabolic pathways, diabetes and cardiovascular diseases, via impaired signaling and metabolism that result in insulin secretion dysfunction, insulin action, and immune responses [1]. Systemic inflammation induces mitochondrial dysfunction, which is involved in both apoptotic and necrotic cell death pathways, and increased glucose uptake by brain tissues, which results in the diversion of glucose to the pentose phosphate pathway that may contribute to oxidative stress by producing excessive superoxide radicals via NADPH oxidase [3, 4]. ROS may be involved in the multistep oncogenesis process at various different phases related to tumor initiation and progression, ROS-related mechanisms during tumor promotion, maintenance of the transformed state through extracellular superoxide radical formation by NADPH oxidase 1, and resistance to oxidative stress signals through membrane-associated catalase expression [7]
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