In vivo Detection of Gastric Cancer in Rats by Electron Paramagnetic Resonance Imaging

Abstract

Electron paramagnetic resonance imaging (EPRI) enables noninvasive spatial mapping of free radical metabolism and has recently been shown to provide in vivo physiologic information regarding alterations in the redox state of tumors and neoplastic tissues. With the use of nitroxide spin probes, it has been shown that certain tumors possess a highly reduced state. To determine whether EPRI can be used for early detection and visualization of gastric carcinoma based on its altered redox metabolism, studies were performed in a rat gastric cancer model induced by 1-methyl-3-nitro-1-nitrosoguanidine. Using a specialized 750 MHz resonator and EPRI instrument, a technique was developed for imaging nitroxide radicals in the whole stomach. In vivo three-dimensional EPRI of the stomach of rats with continuous intravenous administration of nitroxide 3-carboxamido-2,2,5,5-tetramethylpyrrolidine-N-oxyl (3-carbamoyl-proxyl) [3-CP] was performed. Whereas electron paramagnetic resonance images from untreated controls provide a uniform visualization of the stomach mucosa and wall, in the treated rats with gastric cancer, holes were present in the image at the locations of tumors. With localized spectroscopy, it was confirmed that the tumor regions were devoid of signal, and this was largely due to the presence of a more reduced state with rapid reduction of nitroxide. Pharmacokinetic studies indicated that 3-CP in tumors was rapidly reduced to an undetectable level, whereas the 3-CP levels in normal stomach tissue persisted. Near-infrared reflectance measurements of indocyanine green dye uptake indicated that there were no significant differences in tumor versus normal mucosal perfusion. From these results, we concluded that gastric cancer tumors could be distinguished from normal tissue based primarily on the marked difference in their rate of radical metabolism. Because alterations in cellular redox state and radical metabolism are of critical importance in tumor biology and treatment, this methodology should provide an important new tool for the study and visualization of gastric carcinoma and may also be of use in other cancer models.

Comparisons of EPR imaging and T1-weighted MRI for efficient imaging of nitroxyl contrast agents

“…Nitroxyl radicals have been utilized as redox probes in the field of electron paramagnetic resonance (EPR) spectroscopy and imaging [4][5][6][7][8][9][10][11]. EPR can directly detect the absorbance of a microwave/radio frequency by electron spin on nitroxyl radical species.…”

Oxidative Stress Imaging in Live Animals with Techniques Based on Electron Paramagnetic Resonance

“…Three-dimensional images showed a faster rate of reduction nitroxide in the tumor in comparison with normal gastric mucosa. These images were obtained using a surface coil that was introduced into the peritoneal cavity through a small incision (39). …”

Evaluation of sub-microsecond recovery resonators for in vivo electron paramagnetic resonance imaging

“…For small animal investigations, spin probes such as nitroxides (for probing free radical generation and reactions) or triarylmethyl (TAM) radicals (for oxymetry) are used. Employing nitroxides with in vivo EPR, the involvement of free radicals in animal disease models were investigated [1][2][3]. TAM radical, which shows single line EPR spectrum with a narrow and oxygen dependent line width, has been utilized for in vivo oxymetry [4,5].…”