Monitoring of glioblastoma response to a dual PI3K/mTOR inhibitor using hyperpolarized 13C MRSI and 1H MRS

PI3K/Akt/mTOR, one of the important signaling pathways, is activated in ~88% of GBM and different steps in this pathway can serve as therapeutic targets. This study demonstrates non-invasive monitoring of metabolic response to treatment with XL765/SAR245409, a novel dual PI3K/mTOR inhibitor. The inhibition in PI3K/Akt/mTOR signaling pathway leads to changes in levels of 13C MRS-detectable hyperpolarized lactate production from pyruvate and levels of 1H MRS-detectable total choline. Importantly, metabolic changes are associated with significantly longer survival in the case of XL765/SAR245409-treated animals, independent of tumor size.

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