Metabolic response of paediatric-type diffuse high grade glioma cells to PI3K inhibition detected by 2H-MRS

Motivation: Effective treatment response seen in paediatric-type diffuse high grade glioma with conventional MRI can take months to manifest. Goal(s): Evaluation of 2H-MRS for monitoring the metabolism of deuterated glucose in PDHGG cells and assessing early metabolic response to PI3K inhibition. Approach: PIK3R1 mutant neurospheres were treated with a dual PI3K/mTOR inhibitor for 72 and 24 hours, and 2H spectra dynamically acquired in the presence of [6,6-2H2]-glucose. Results: Treatment significantly reduced glycolytic rates at both timepoints. At 24 hours there was no difference in cell number or viability, highlighting the potential of 2H-MRS to provide an early biomarker of response. Impact: Establishing acute treatment-induced changes in the glycolytic rate of PDHGG neurospheres using 2H-MRS provides confidence in the sensitivity of deuterium metabolic imaging for assessing the early response of orthotopic PDHGG models to PI3K inhibition in vivo.