4.8 Article

Rapid hyperpolarization and purification of the metabolite fumarate in aqueous solution

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2025383118

Keywords

hyperpolarization; parahydrogen; metabolism; MRI; biomarker

Funding

  1. European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant [766402]
  2. European Research Council [786707]
  3. European Union's Horizon 2020 Research and Innovation Program under FETOPEN [858149]
  4. Compagnia di San Paolo (Athenaeum Research Grant 2016) [CSTO164550]
  5. German Research Council [BU 911/22-2, BU 911/29-1]
  6. research unit NanoKat at the TU Kaiserslautern
  7. NSF [CHE-1709944]
  8. Johannes-Gutenberg University Mainz internal grant
  9. European Research Council (ERC) [786707] Funding Source: European Research Council (ERC)

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This study discusses the techniques of hyperpolarizing fumarate using dissolution dynamic nuclear polarization and parahydrogen-induced polarization, as well as the method of purifying pure solid fumarate from impurities through acid precipitation.
Hyperpolarized fumarate is a promising biosensor for carbon-13 magnetic resonance metabolic imaging. Such molecular imaging applications require nuclear hyperpolarization to attain sufficient signal strength. Dissolution dynamic nuclear polarization is the current state-of-the-art methodology for hyperpolarizing fumarate, but this is expensive and relatively slow. Alternatively, this important biomolecule can be hyperpolarized in a cheap and convenient manner using parahydrogen-induced polarization. However, this process requires a chemical reaction, and the resulting solutions are contaminated with the catalyst, unreacted reagents, and reaction side-product molecules, and are hence unsuitable for use in vivo. In this work we show that the hyperpolarized fumarate can be purified from these contaminants by acid precipitation as a pure solid, and later redissolved to a desired concentration in a clean aqueous solvent. Significant advances in the reaction conditions and reactor equipment allow for formation of hyperpolarized fumarate at C-13 polarization levels of 30-45%.

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