Real-Time Nuclear Magnetic Resonance Detection of Fumarase Activity Using Parahydrogen-Hyperpolarized [1-13C]Fumarate

J Am Chem Soc. 2019 Dec 26;141(51):20209-20214. doi: 10.1021/jacs.9b10094. Epub 2019 Dec 10.

Abstract

Hyperpolarized fumarate can be used as a probe of real-time metabolism in vivo, using carbon-13 magnetic resonance imaging. Dissolution dynamic nuclear polarization is commonly used to produce hyperpolarized fumarate, but a cheaper and faster alternative is to produce hyperpolarized fumarate via PHIP (parahydrogen-induced polarization). In this work, we trans-hydrogenate [1-13C]acetylene dicarboxylate with para-enriched hydrogen using a commercially available Ru catalyst in water to produce hyperpolarized [1-13C]fumarate. We show that fumarate is produced in 89% yield, with succinate as a side product in 11% yield. The proton polarization is converted into 13C magnetization using a constant adiabaticity field cycle, and a polarization level of 24% is achieved using 86% para-enriched hydrogen gas. We inject the hyperpolarized [1-13C]fumarate into cell suspensions and track the metabolism. This work opens the path to greatly accelerated preclinical studies using fumarate as a biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon Isotopes
  • Fumarate Hydratase / analysis*
  • Fumarate Hydratase / metabolism
  • Fumarates / chemistry*
  • Fumarates / metabolism
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular*
  • Time Factors

Substances

  • Carbon Isotopes
  • Fumarates
  • Fumarate Hydratase
  • Carbon-13