Imaging TCA Cycle Metabolism by PHIP Hyperpolarization of 1,3C Succinate In Vivo

In vivo metabolic imaging of reactions in the Krebs TCA cycle using hyperpolarization was performed using ¹³C deuterated fumarate that was hydrogenated to 1-¹³C succinate and hyperpolarized to ~8% by PHIP. On tail-vein injection of hyperpolarized succinate in tumor-bearing mice, hyperpolarized metabolic products were detected with 20,000 fold increased sensitivity over 3-5 minutes. The metabolic fate of hyperpolarized succinate differed in two tumors: in RENCA renal carcinoma metabolic products malate, fumarate, glutamate and citrate were defined, and in Lymphoma A20 the metabolic products were limited to malate. These differences are tentatively assigned to the presence of hypoxia inducing factor HIF1α.