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Abstract #3056

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

Declan J. Bolster1, James O'Keeffe1, Upasana Roy1, Aidan M. Michaels2, Rebecca Rogers3, Diana Martins Carvalho3, Maggie Lui4, Amin Mirza4, Yann Jamin1, Carol Box1, Chris Jones5, Thomas Eykyn2, Simon Robinson1, and Jessica K. R. Boult1
1Division of Radiotherapy & Imaging, Institute of Cancer Research, London, United Kingdom, 2School of Biomedical Engineering and Imaging Sciences, Kings College London, London, United Kingdom, 3Division of Molecular Pathology, Institute of Cancer Research, London, United Kingdom, 4Cancer Therapeutics Unit, Institute of Cancer Research, London, United Kingdom, 5Molecular Pathology, Institute of Cancer Research, London, United Kingdom

Synopsis

Keywords: Deuterium, Deuterium, Preclinical

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.

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