Assessment of tissue redox status using metabolic responsive contrast agents and magnetic resonance imaging

Abstract

Regulation of tissue redox status is important to maintain normal physiological conditions in the living body. Disruption of redox homeostasis may lead to oxidative stress and can induce many pathological conditions such as cancer, neurological disorders, and aging. Therefore, imaging of tissue redox status could have clinical applications. Redox imaging employing magnetic resonance imaging (MRI) with nitroxides as cell permeable redox sensitive contrast agents has been used for non-invasive monitoring of tissue redox status in animal models. The redox imaging applications of nitroxide EPRI and MRI are reviewed here, with a focus on application of tumor redox status monitoring. While particular emphasis has been placed on differences in the redox status in tumors compared selected normal tissues, the technique possesses the potential to have broad applications to the study of other disease states, inflammatory processes, and other circumstances where oxidative stress is implicated.

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

“…In addition to their use as spin probes in EPR detection, identification of free radicals, and the study of tumor hypoxia (296,297), magnetic resonance imaging with nitroxides, as cell-permeable redox-sensitive contrast agents, has been used for noninvasive monitoring of tissue redox status in animal models (156,160). The imaging technique uses differential reduction of nitroxides in hypoxic and normal oxygenated tissue.…”

Hepatic Reduction of Carbamoyl-PROXYL in Ferric Nitrilotriacetate Induced Iron Overloaded Mice: An <i>in Vivo</i> ESR Study

“…3) The nitroxyl spin probes react with hydroxyl radicals, superoxide anion 4) and various endogenous reducing agents, such as ascorbic acid, glutathione (GSH), reduced form of nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), [5][6][7] resulting in the loss of ESR signal. Thus, the rate of ESR signal decay of nitroxyl spin probes have been used to monitor free radical production and redox status in various animal models, including tumor inoculated in mouse footpads, 8) indomethacin-induced gastric ulcers, 9) rheumatoid arthritis, 10) hypertension, 11) cerebral ischemia-reperfusion, 12) lung injury caused by diesel exhaust particles, 13) and radiationinduced oxidative injury.…”

Mitochondrial Dysfunction and Redox Imbalance as a Diagnostic Marker of “Free Radical Diseases”

“…The radical and oxoammonium forms act as an efficient redoxpair via reversible one-electron redox reactions, while hydroxylamine and nitroxide radical forms do not constitute an effective redox-pair. This feature determines nitroxide radicals as perfect compounds for imaging of intracellular redox balance (92,94). This redox cycle can be detected, using magnetic resonance imaging techniques as electronparamagnetic resonance (EPR) spectroscopy and imaging (EPRI), as well as magnetic resonance imaging (MRI).…”