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Abstract #4723

Early MR-detectable biomarkers of mutant IDH inhibition in patient-derived low-grade gliomas in vivo

Marina Radoul1, ChloƩ Najac1, Donghyun Hong1, Anne Marie Gillespie1, Pavithra Viswanath1, Russell O. Pieper2,3, Joseph F. Costello2, and Sabrina M. Ronen1,3
1Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, 2Neurological 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

Low-grade glioma (LLG) patients have a relatively long-term survival of ~13 years but these tumors always recur. Since IDH mutations are present in >80% of LGGs, inhibition of mutant IDH activity is being tested as a new therapeutic approach. Here, we investigated response to mutant IDH inhibition by AG-881 in orthotopic LGG mouse models. Using in vivo 1H MRS we detected, in addition to a decrease in 2-HG, an early increase in both glutamate and glutamine/glutamate that were associated with subsequent tumor shrinkage. This identifies potential early metabolic biomarkers of LGG response to mutant IDH inhibition.

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