NEIM-11 DEUTERIUM METABOLIC IMAGING (DMI) DETECTS A LARGER WARBURG EFFECT IN HIGH-GRADE BRAIN TUMORS AND IN IDH WILD TYPE GLIOMAS

Abstract

Abstract BACKGROUND The Warburg Effect (WE) is a metabolic change in which tumors favor glycolysis over oxidative phosphorylation and has been linked to cancer aggressiveness. Mutations in the isocitrate dehydrogenase (IDH) genes in gliomas are associated with improved outcomes. We deployed a magnetic resonance (MR) spectroscopic imaging technique coined Deuterium Metabolic Imaging (DMI) to measure the WE in multiple brain tumor types. METHODS Twenty-one patients underwent DMI, acquired on a Bruker 4T MR scanner after oral administration of 0.75g/kg of deuterated glucose. The WE was defined as the ratio of deuterated lactate, representing glycolysis, over deuterated glutamate and glutamine, representing oxidative phosphorylation. We devised an interval scale from 0 to 2 for the WE RESULTS The Wilcoxon rank sum test was performed to detect differences between groups. RESULTS The WE measurements for the largest groups, by diagnosis, showed: glioblastoma (n=9, mean=1.67); astrocytoma, IDH-mutant, WHO grade 3 (n=2, mean=0.25); oligodendroglioma, WHO grade 3 (n=3, mean=0.5); low grade glioma, IDH-mutant (n=2, mean=0); and meningioma, WHO grade 2 (n=2, mean=0). The WE for high-grade tumors (n=15, mean=1.27) was significantly different from the WE for low-grade tumors (n=5, mean=0), with a p=0.010. The WE for IDH wild type gliomas (n=9, mean=1.67) was significantly different from the WE for IDH-mutant gliomas (n=9, mean=0.44), with a p=0.007. Analysis is ongoing. CONCLUSIONS DMI successfully and non-invasively detects the WE in many types of brain tumors. The WE was larger in high-grade tumors as compared to low-grade tumors, and the WE was larger in IDH wild type gliomas as compared to IDH-mutant gliomas. If validated with future studies, our results suggest that DMI is a useful tool to measure differences in the metabolism of brain tumors with different clinical behaviors.