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 13C polarization levels of 30–45%.

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 <i>in vivo</i>. 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%.

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 <i>in vivo</i>. 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%.

Parahydrogen‐based nuclear spin hyperpolarization allows various magnetic‐resonance applications, and it is particularly attractive because of its technical simplicity, low cost, and ability to quickly (in seconds) produce large volumes of hyperpolarized material. Although many parahydrogen‐based techniques have emerged, some of them remain unexplored due to the lack of careful optimization studies. In this work, we investigate and optimize a novel parahydrogen‐induced polarization (PHIP) technique that relies on proton exchange referred to below as PHIP‐relay. An INEPT (insensitive nuclei enhanced by polarization transfer) sequence is employed to transfer polarization from hyperpolarized protons to heteronuclei ( 15 ${^{15} }$ N and 13 ${^{13} }$ C) and nuclear signals are detected using benchtop NMR spectrometers (1 T and 1.4 T, respectively). We demonstrate the applicability of the PHIP‐relay technique for hyperpolarization of a wide range of biochemicals by examining such key metabolites as urea, ammonium, glucose, amino acid glycine, and a drug precursor benzamide. By optimizing chemical and NMR parameters of the PHIP‐relay, we achieve a 17,100‐fold enhancement of 15 ${^{15} }$ N signal of [ 13 ${^{13} }$ C, 15 ${^{15} }$ N 2 ${_2 }$ ]‐urea compared to the thermal signal measured at 1 T. We also show that repeated measurements with shorter exposure to parahydrogen provide a higher effective signal‐to‐noise ratio compared to longer parahydrogen bubbling.