Real-Time in Vivo Detection of H 2 O 2 Using Hyperpolarized 13 C-Thiourea

ACS Chem Biol. 2017 Jul 21;12(7):1737-1742. doi: 10.1021/acschembio.7b00130. Epub 2017 Jun 5.

Abstract

Reactive oxygen species (ROS) are essential cellular metabolites widely implicated in many diseases including cancer, inflammation, and cardiovascular and neurodegenerative disorders. Yet, ROS signaling remains poorly understood, and their measurements are a challenge due to high reactivity and instability. Here, we report the development of 13C-thiourea as a probe to detect and measure H2O2 dynamics with high sensitivity and spatiotemporal resolution using hyperpolarized 13C magnetic resonance spectroscopic imaging. In particular, we show 13C-thiourea to be highly polarizable and to possess a long spin-lattice relaxation time (T1), which enables real-time monitoring of ROS-mediated transformation. We also demonstrate that 13C-thiourea reacts readily with H2O2 to give chemically distinguishable products in vitro and validate their detection in vivo in a mouse liver. This study suggests that 13C-thiourea is a promising agent for noninvasive detection of H2O2 in vivo. More broadly, our findings outline a viable clinical application for H2O2 detection in patients with a range of diseases.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carbon Isotopes / analysis
  • DNA / chemistry
  • Hydrogen Peroxide / analysis*
  • Lipids / chemistry
  • Liver / metabolism
  • Magnetic Resonance Imaging
  • Mice
  • Oxidative Stress
  • Proteins / chemistry
  • Reactive Oxygen Species
  • Spectrum Analysis
  • Thiourea / chemistry*
  • Thiourea / metabolism

Substances

  • Carbon Isotopes
  • Lipids
  • Proteins
  • Reactive Oxygen Species
  • DNA
  • Hydrogen Peroxide
  • Thiourea