Interrogating Tricarboxylic Acid Cycle: A Comparative Study by Hyperpolarized Succinic Acid & Its Diethylester

Pratip Bhattacharya¹, Niki Zacharias¹, Henry Chan¹, Napapon Sailasuta¹, Larry W. Robertson¹, Alan Epstein², Brian D. Ross¹

The goal of this work is to interrogate the succinate level in the cytosol by hyperpolarization of succinate, a key metabolite of Tricarboxylic Acid Cycle (TCA) and its diethyl ester derivate. Succinate Dehydrogenase (SDH)-catalyzes the oxidation of succinate to fumarate with the reduction of ubiquinone to ubiquinol and is an oncogene defined in many cancers. Here we demonstrate different metabolic profiles in vivo using two molecules with slight variations but with very different uptake rates. Hyperpolarized diethyl ester of succinic acid (diethylsuccinate) is taken up rapidly in vivo in both normal and tumor bearing mice, while hyperpolarized succinic acid is apparently taken up only in some tumor bearing animals. The results underscore the importance of chemical modification in choosing molecular targets to achieve desired metabolic imaging using hyperpolarization.