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

preprint
submitted on 13.09.2019 and posted on 17.09.2019 by James Eills, Eleonora Cavallari, Carla Carrera, Dmitry Budker, Silvio Aime, Francesca Reineri
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 25% 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.

Funding

Marie Skłodowska-Curie Grant Agreement No. 766402

Compagnia di San Paolo (Athenaeum Research 2016, n. CSTO164550)

History

Email Address of Submitting Author

eills@uni-mainz.de

Institution

Johannes Gutenberg Universität Mainz

Country

Germany

ORCID For Submitting Author

0000-0001-8468-6860

Declaration of Conflict of Interest

The authors declare no conflict of interest.

Licence

Exports