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Abstract #4173

MCT down-regulation contributes to reduced conversion of hyperpolarized [1-13C]-pyruvate to [1-13C]-lactate in IDH1 mutant glioma cells

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.

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