Abstract #4315

Hyperpolarized 5-13C-Glutamate metabolism as a biomarker of IDH1 mutant glioma response to temozolomide therapy

Elavarasan Subramani¹, Chloe Najac¹, Georgios Batsios¹, Pavithra Viswanath¹, Marina Radoul¹, Anne Marie Gillespie¹, Russell O Pieper^2,3, and Sabrina M Ronen^1,3

¹Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ²Department of Neurological Surgery, Helen Diller Research Center, University of California San Francisco, San Francisco, CA, United States, ³Brain Tumor Research Center, University of California San Francisco, San Francisco, CA, United States

The alkylating agent temozolomide (TMZ), previously used only in the treatment of high-grade glioblastoma, is now being considered for the treatment of low-grade glioma that are driven by mutations in the cytosolic isocitrate dehydrogenase 1 (IDH1) gene. However, early detection of response remains a challenge. 1H and hyperpolarized ¹³C magnetic resonance spectroscopy-based metabolic profiling of cells genetically engineered to express mutant IDH1 and treated with TMZ showed significant alterations in metabolites majorly related to the tricarboxylic acid cycle, and identified hyperpolarized 5-¹³C-glutamate metabolism as an indicator of response. These findings hold potential for assessing response of IDH1 mutant cells to TMZ therapy.

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