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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