Abstract #0019

Early noninvasive metabolic biomarkers of mutant IDH inhibition in low-grade glioma models

Marina Radoul¹, Donghyun Hong¹, Anne Marie Gillespie¹, Chloé Najac¹, Pavithra Viswanath¹, Russell O. Pieper^2,3, Joseph Costello², H. Artee Luchman⁴, and Sabrina M. Ronen^1,3

¹Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ²Neurological Surgery UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, United States, ³Brain Tumor Research Center, University of California San Francisco, San Francisco, CA, United States, ⁴Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada

Targeting mutant IDH, which is present in ~80% of glioma, is being tested as a new therapeutic approach. In the current study, we investigated metabolic alterations in response to mutant IDH inhibition by either AG-881 or BAY-1436032 in orthotopic patient-derived glioma models. Using high resolution in vivo ¹H MRS we detected, in addition to a decrease in 2HG, an early increase in glutamate and the combined glutamine/glutamate signals. These were associated with slowdown of tumor growth and ultimately longer animal survival. This identifies potential early metabolic biomarkers of glioma response to mutant IDH inhibition.

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