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Abstract #0495

Metabolic reprogramming associated with IDH1-targeted treatments in low-grade glioma cell models: a 1H and 13C MRS study

Abigail R Molloy1, Chloé Najac1, Aliya Lakhani1, Elavarasan Subramani1, Georgios Batsios1, Anne Marie Gillespie1, Russell O Pieper2,3, Pavithra Viswanath1, and Sabrina M Ronen1,3
1Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, 2Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States, 3Brain Tumor Research Center, University of California, San Francisco, San Francisco, CA, United States

Mutant IDH1 (IDH1mut) drives glioma development, and targeted IDH1mut inhibitors show promising results in clinical trials. However, treatment is not associated with tumor shrinkage, and there is an urgent need for early imaging biomarkers of response. Our studies in IDH1mut-expressing glioma cells indicate that treatment with IDH1mut inhibitors leads to 1H and 13C-MRS-detectable metabolic changes. Specifically, we show a decrease in 2-HG and increase in glutamate, as well as an increase in metabolic flux from glutamine to glutamate. Furthermore, hyperpolarized [1-13C] α-ketoglutarate can probe these alterations in metabolism. This identifies potential non-invasive biomarkers of response to IDH1mut inhibition in glioma.

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