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Abstract #0677

Proton and hyperpolarized 13C MRS based biomarkers response to the BAY-1436032 IDH inhibitor in cell and in vivo glioma models

Donghyun Hong1, Marina Radoul1, Noriaki Minami1, Anne Marie Gillespie1, Russell O. Pieper1, Joseph Costello1, Pavithra Viswanath1, and Sabrina M. Ronen1
1University of California, San Francisco, San Francisco, CA, United States

Synopsis

Mutant IDH1 inhibitor treatment is currently in clinical trials for glioma patients. Therefore, in vivo biomarkers are needed to assess early therapeutic responses. Here we treated mutant IDH1-expressing cells and animals with patient-derived mutant IDH1 brain tumors with the emerging inhibitor BAY-1436032. Using 1H MRS we found a significant decrease in 2HG that was accompanied by an increase in glutamate and phosphocholine, and using 13C MRS we detected a significant decrease in 2HG and a significant increase in glutamate produced from hyperpolarized [1-13C] α-ketoglutarate in cell and animal models.

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Keywords