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.
Keywords