Pavithra Viswanath1, Jose Izquierdo-Garcia1, Chloe Najac1, Larry Cai1, Russell Pieper2, and Sabrina M Ronen1
1Radiology, University of California San Francisco, San Francisco, CA, United States, 2Neurological Surgery, University of California San Francisco, San Francisco, CA, United States
In
this study we used hyperpolarized 13C-MRS to investigate pyruvate to
lactate flux in IDH1 mutant cells. We found reduced hyperpolarized [1-13C]-lactate
production from hyperpolarized [1-13C]-pyruvate in IDH1 mutant cells
compared to wild-type. While there was no difference in lactate dehydrogenase A
activity or NAD+/NADH, IDH1 mutant cells and patient samples showed reduced
expression of monocarboxylate transporters MCT1 and MCT4. Comparison of
hyperpolarized [1-13C]-lactate production between IDH1 wild-type and
mutant lysates confirmed that reduced MCT expression was responsible for
reduced hyperpolarized [1-13C]-lactate production. Thus, our study
indicates that reduced MCT expression is a metabolic feature of the IDH1 mutation.
