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Abstract #0656

Noninvasive Monitoring of PI3K Inhibition: Reduced Hyperpolarized Lactate and PC Are Independent of Genetic Background in Glioblastoma

Humsa S. Venkatesh1, Charles D. James2, Daphne A. Haas-Kogan2, Sabrina M. Ronen1

1Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States; 2Neurological Surgery, University of California, San Francisco

As the PI3K pathway is activated in 88% of glioblastomas, it is the target of several novel therapies. The purpose of this investigation is to study GBM cells with different genetic backgrounds in order to establish hyperpolarized lactate and PC as biomarkers of PI3K inhibition. Two inhibitors of PI3K signaling and agents that do not affect signaling were investigated. Hyperpolarized lactate and PC dropped only when signaling was inhibited and this observation was mechanistically linked to a drop in HIF-1, which controls expression of LDH and choline kinase. This suggests an application for these metabolites as noninvasive biomarkers for PI3K-targeted anticancer treatments.