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 Pieper^2,3, Pavithra Viswanath¹, and Sabrina M Ronen^1,3

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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