Crystal E. Harrison1,2, Ralph J. DeBerardinis3,4, Ashish K. Jindal1, Chendong Yang3, A Dean Sherry1,5, Craig R. Malloy1,6
1Advanced Imaging Research Center, UT Southwestern, Dallas, TX, United States; 2Physics, UT Dallas, Richardson, TX, United States; 3Pediatrics, UT Southwestern, Dallas, TX, United States; 4McDermott Center for Human Growth and Development, UT Southwestern, Dallas, TX, United States; 5Chemistry, UT Dallas, Richardson, TX, United States; 6Veterans Affairs, NorthTexas Health Care System, Dallas, TX, United States
While most research in cancer metabolism has focused on lactate formation (the Warburg effect), less is known about the mitochondrial pathways utilized during cell growth. Hyperpolarized [1-13C]-pyruvate provides insight into both the Warburg effect and mitochondrial metabolism, including activity of pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC). To combine the sensitivity of hyperpolarization with the precision of isotopomer analysis, we pre-incubated glioblastoma cells with [3-13C]-pyruvate prior to a short incubation with hyperpolarized [1-13C]-pyruvate. Using this technique, we observed real-time accumulation of hyperpolarized, 13C-labeled lactate and bicarbonate, and determined that the latter arose from the direct activity of PDH.