Therapeutic response assessment to IDH inhibitor using hyperpolarized [5-12C-1-13C]α-ketoglutarate MRSI in rat models of low-grade glioma

Hyperpolarized [1-13C]α-ketoglutarate is useful for monitoring 2HG and glutamate production but has limited SNR and the [5-13C]α-ketoglutarate natural abundance peak is within 0.1ppm of 2HG. To address these challenges, this study investigated the utility of HP [5-12C-1-13C]α-ketoglutarate to monitor 2HG and glutamate production as biomarkers of response to treatment with the mutant IDH inhibitor BAY-1436032 in an in vivo rat glioma model using an optimized acquisition strategy. We were able to clearly monitor the dynamic localized production of both 2HG and glutamate in vivo in real-time, and early metabolic changes predicted enhanced survival.