In vivo detection of gastric cancer in rats by electron paramagnetic resonance imaging

Tomiko Mikuni, Guanglong He, Sergey Petryakov, Mohanad M. Fallouh, Yuanmu Deng, Ryu Ishihara, Periannan Kuppusamy, Masaharu Tatsuta, Jay L. Zweier

Research output: Contribution to journalArticle

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-carbox-amido-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.

Original languageEnglish (US)
Pages (from-to)6495-6502
Number of pages8
JournalCancer Research
Volume64
Issue number18
DOIs
StatePublished - Sep 15 2004
Externally publishedYes

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Electron Spin Resonance Spectroscopy
Stomach Neoplasms
Stomach
Neoplasms
Oxidation-Reduction
Nitrosoguanidines
Carcinoma
Indocyanine Green
Intravenous Administration
Free Radicals
Spectrum Analysis
Mucous Membrane
Coloring Agents
Pharmacokinetics
Perfusion

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mikuni, T., He, G., Petryakov, S., Fallouh, M. M., Deng, Y., Ishihara, R., ... Zweier, J. L. (2004). In vivo detection of gastric cancer in rats by electron paramagnetic resonance imaging. Cancer Research, 64(18), 6495-6502. https://doi.org/10.1158/0008-5472.CAN-04-0319

In vivo detection of gastric cancer in rats by electron paramagnetic resonance imaging. / Mikuni, Tomiko; He, Guanglong; Petryakov, Sergey; Fallouh, Mohanad M.; Deng, Yuanmu; Ishihara, Ryu; Kuppusamy, Periannan; Tatsuta, Masaharu; Zweier, Jay L.

In: Cancer Research, Vol. 64, No. 18, 15.09.2004, p. 6495-6502.

Research output: Contribution to journalArticle

Mikuni, T, He, G, Petryakov, S, Fallouh, MM, Deng, Y, Ishihara, R, Kuppusamy, P, Tatsuta, M & Zweier, JL 2004, 'In vivo detection of gastric cancer in rats by electron paramagnetic resonance imaging', Cancer Research, vol. 64, no. 18, pp. 6495-6502. https://doi.org/10.1158/0008-5472.CAN-04-0319
Mikuni T, He G, Petryakov S, Fallouh MM, Deng Y, Ishihara R et al. In vivo detection of gastric cancer in rats by electron paramagnetic resonance imaging. Cancer Research. 2004 Sep 15;64(18):6495-6502. https://doi.org/10.1158/0008-5472.CAN-04-0319
Mikuni, Tomiko ; He, Guanglong ; Petryakov, Sergey ; Fallouh, Mohanad M. ; Deng, Yuanmu ; Ishihara, Ryu ; Kuppusamy, Periannan ; Tatsuta, Masaharu ; Zweier, Jay L. / In vivo detection of gastric cancer in rats by electron paramagnetic resonance imaging. In: Cancer Research. 2004 ; Vol. 64, No. 18. pp. 6495-6502.
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