Imaging thiol redox status in murine tumors in vivo with rapid-scan electron paramagnetic resonance

J Magn Reson. 2017 Mar:276:31-36. doi: 10.1016/j.jmr.2016.12.015. Epub 2016 Dec 31.

Abstract

Thiol redox status is an important physiologic parameter that affects the success or failure of cancer treatment. Rapid scan electron paramagnetic resonance (RS EPR) is a novel technique that has shown higher signal-to-noise ratio than conventional continuous-wave EPR in in vitro studies. Here we used RS EPR to acquire rapid three-dimensional images of the thiol redox status of tumors in living mice. This work presents, for the first time, in vivo RS EPR images of the kinetics of the reaction of 2H,15N-substituted disulfide-linked dinitroxide (PxSSPx) spin probe with intracellular glutathione. The cleavage rate is proportional to the intracellular glutathione concentration. Feasibility was demonstrated in a FSa fibrosarcoma tumor model in C3H mice. Similar to other in vivo and cell model studies, decreasing intracellular glutathione concentration by treating mice with l-buthionine sulfoximine (BSO) markedly altered the kinetic images.

Keywords: EPR imaging; Electron paramagnetic resonance; Glutathione; Rapid scan EPR; Thiol redox status.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain Neoplasms / diagnostic imaging*
  • Buthionine Sulfoximine / chemistry
  • Diagnostic Imaging / methods*
  • Disulfides / chemistry
  • Electron Spin Resonance Spectroscopy / methods*
  • Female
  • Fibrosarcoma / diagnostic imaging*
  • Glutathione / metabolism
  • Imaging, Three-Dimensional
  • Kinetics
  • Mice
  • Mice, Inbred C3H
  • Neoplasms, Experimental / diagnostic imaging*
  • Neoplasms, Experimental / metabolism
  • Nitrogen Oxides / chemistry
  • Oxidation-Reduction
  • Signal-To-Noise Ratio
  • Spin Labels / chemical synthesis

Substances

  • Disulfides
  • Nitrogen Oxides
  • Spin Labels
  • Buthionine Sulfoximine
  • Glutathione