Rapid Hyperpolarization and Purification of the Metabolite Fumarate in Aqueous Solution

Hyperpolarized fumarate is a promising agent for carbon-13 magnetic resonance metabolic imaging of cellular necrosis. 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 hyperpolarized fumarate 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 at a chosen concentration in a clean aqueous solvent. Significant advances in the reaction conditions and reactor equipment allow us to form hyperpolarized fumarate at a concentration of several hundred millimolar, at ¹³C polarization levels of 30-45%.