Organ specific mapping of in vivo redox state in control and cigarette smoke-exposed mice using EPR/NMR co-imaging

Abstract

In vivo mapping of alterations in redox status is important for understanding organ specific pathology and disease. While electron paramagnetic resonance imaging (EPRI) enables spatial mapping of free radicals, it does not provide anatomic visualization of the body. Proton MRI is well suited to provide anatomical visualization. We applied EPR/NMR co-imaging instrumentation to map and monitor the redox state of living mice under normal or oxidative stress conditions induced by secondhand cigarette smoke (SHS) exposure. A hybrid co-imaging instrument, EPRI (1.2 GHz) / proton MRI (16.18 MHz), suitable for whole-body co-imaging of mice was utilized with common magnet and gradients along with dual EPR/NMR resonators that enable co-imaging without sample movement. The metabolism of the nitroxide probe, 3–carbamoyl–proxyl (3-CP), was used to map the redox state of control and SHS-exposed mice. Co-imaging allowed precise 3D mapping of radical distribution and reduction in major organs such as the heart, lungs, liver, bladder and kidneys. Reductive metabolism was markedly decreased in SHS-exposed mice and EPR/NMR co-imaging allowed quantitative assessment of this throughout the body. Thus, in vivo EPR/NMR co-imaging enables in vivo organ specific mapping of free radical metabolism and redox stress and the alterations that occur in the pathogenesis of disease.

Measurement of Reactive Oxygen Species, Reactive Nitrogen Species, and Redox-Dependent Signaling in the Cardiovascular System

“…100–102 This oxy-redoximetric assay is highly promising, and ex vivo cardiac applications have been performed with nitroxide probes. 103 …”

Comparative Study of the Reduction Process of Different Ring Structured Nitroxyl Spin Probes: An Electron Spin Resonance Study

“…The ESR signal intensity values were fitted with a simple model of an exponential decay equation and an added constant offset, which is used to determine the half life time (t 1/2 ) and the decay rate (1/τ) of the nitroxyl radical in ascorbic acid [42,43]. The ESR spectral intensity I (t) can be expressed as The correlation coefficient of the above curve fitting shows the best correlation (R 2 >0.99).…”

Electron Spin Resonance Spectroscopy Studies on Reduction Process of Nitroxyl Radicals used in Molecular Imaging

“…The ESR signal intensity values were fitted with a simple model of an exponential decay equation and an added constant offset, which is used to determine the half life time (t 1/2 ) and the decay rate (1/τ) of the nitroxyl radical in ascorbic acid [10,40]. The ESR spectral intensity I (t) can be expressed as The half life time and decay rate values for TEMPONE, TEMPO and TEMPOL are listed in Table 3.…”

“…The measurement of ESR signal intensity is equal to the measurement of organ reducing activity against radicals, which is a major factor of organ antioxidative activity. Therefore, the measurement of reducing or oxidizing Nitroxyl Radicals used in Molecular Imaging activity by ESR technique using nitroxyl spin probes may provide various information about the reductive or oxidative environments in living tissues, free radical metabolism, in vivo redox status and biological status [10][11][12][13][14][15][16][17][18][19][20][21][22].…”