Simultaneous 280 MHz EPR imaging of rat organs during nitroxide free radical clearance

Abstract

A radio frequency (RF) (280 MHz) electron paramagnetic resonance (EPR) spectroscopy and imaging apparatus has been used to localize a pyrrolidine nitroxide free radical in the rat abdomen and thorax. The nitroxide 2,2.5.5,-tetramethylpyrrolidine-1-oxyl-3- carboxylic acid (PCA) had a whole body monoexponential decay with half-life of 13.3 +/- 0.7 (n = 4), 19.4 +/- 0.2 (n = 3), and 23 +/- 2 (n = 6) min for 1, 2, and 3 mmol/kg PCA, respectively. Up to seven one-dimensional longitudinal projections were collected on six rats in the presence of a 8 mT/m field gradient. With an injection dose of 3 mmol/kg, PCA half-lives were 19 +/- 1, 17 +/- 2, and 22 +/- 2 min (n = 6) in the lower abdomen, in the liver, and in the thorax, respectively. Thorax half-life was significantly longer than liver half-life. Sequential two-dimensional images of PCA distribution in a plane longitudinal to the rat body were obtained from eight spectra in the presence of a gradient of 12 mT/m (acquisition time 5 min; spatial resolution 8 mm). After 7 min, the nitroxide was detectable in the left side of the thorax area, but it was mostly localized in the liver. PCA was more uniformly distributed in the image collected after 17 min.

Application of in vivo EPR in brain research: monitoring tissue oxygenation, blood flow, and oxidative stress

“…In vivo EPR imaging was first performed using an exogenous, synthetic, and stable free radical that was locally administered to small animals. 27 With the recent improvement of low-frequency EPR instrumentation and the synthesis of better imaging agents, many exciting results have been obtained. For example, imaging of the abdominal region of mice treated with lipopolysaccharide demonstrated the presence of spin trapped NO; 28 three-dimensional spatial and two-dimensional spectral-spatial imaging of charcoal in the GI tract of a living mouse demonstrated the oxygen gradient in the organ; 29 imaging of rat brain under kainic acid-induced seizure indicated that the oxidative stress in the hippocampus and striatum is enhanced, but is not in cerebral cortex; 30 and imaging of tumor-bearing legs of mice showed oxygen concentration images with high resolution in space (1 mm) and pO 2 ($3 torr).…”

Spin probes for electron paramagnetic resonance imaging

“…For example, a charged nitroxide will not cross the plasma membrane and thus can be used to measure the concentration of oxygen in the extracellular compartment; a neutral nitroxide will be distributed throughout the intracellular and extracellular environments [44,45] . Nitroxides have also played a key role in the field of EPRI, where numerous organs of the rat have been investigated [46][47][48] . EPRI of the abdominal region of mice REVIEW ORGANIC CHEMISTRY treated with lipopolysaccharide was achieved in the presence of spin-trapped NO.…”

Spatially Resolved Biologic Information from In Vivo EPRI, OMRI, and MRI

“…One-dimensional EPR spectra of a nitroxyl radical, TEM- (11). After that, 2D or 3D EPRI studies in mice or rats were reported from several groups (2,4,41,103). A variety of EPRI systems and equipment for biologic samples were developed by each group for their experimental purpose (3, 13-15, 24, 29, 47, 82, 83, 95).…”