Enhanced Solubility and Polarization of 13C-fumarate with Meglumine Allows in vivo Detection of Renal Gluconeogenesis

Motivation: Clinical translation of many hyperpolarized substrates, including 13C-fumarate, has been obstructed by its low solubility in water, causing rapid precipitation of the substrates after dissolution when prepared in conventional glassing solvents. Goal(s): The goal of this study was to enhance water solubility and glassing properties of fumarate. Approach: We introduced a new formulation of fumarate for DNP by using meglumine as a counterion. Results: Meglumine significantly improved the polarization performance of fumarate with excellent solubility and glassing properties and previously invisible products along gluconeogenesis were observed in rat kidneys in vivo. Impact: The solubilizing and vitrifying effect of meglumine counterion is not limited to fumarate. It is applicable to other 13C- and 15N-labeled compounds such as carboxylic acids and amino acids that have poor solubility and can form meglumine salts or adducts.