TMET-20. A METABOLIC BIOMARKER IN GLIOBLASTOMA: A PROMISING APPLICATION OF CO-POLARIZED [1-13C]PYRUVATE AND [1-13C]DEHYDROASCORBATE

Abstract BACKGROUND Noninvasive biomarkers for treatment response in glioblastoma are needed to improve patient outcomes. Our understanding of redox biology in treatment resistance is rapidly evolving, and interrogation of tumor metabolism represents an ideal opportunity to meet this need. In this study, the utility of co-hyperpolarized [1-13C]pyruvate and [1-13C]dehydroascorbate (HP PA/DHA) to simultaneously evaluate brain tumor metabolism and oxidative stress in orthotopically implanted mice is investigated. METHODS To characterize HP PA/DHA, mice were treated with 0-4mM diethyl maleate and 1D slab dynamic acquisitions were performed over the mouse brain. As an initial evaluation of the utility of HP DHA/PA in brain tumors, athymic nude mice (n=8) underwent orthotopic U87 glioblastoma implantation. After treatment with 8Gy in one fraction, mice were injected with HP DHA/PA dissolved in D2O. T2-weighted and 13C Chemical Shift Imaging sequences were obtained on a 3T MRI using a quadrature double-tuned 1H/13C volume coil. RESULTS HP DHA/PA detected differential lactate and vitamin C generation over the mouse brain. Treatment with diethyl maleate, which depletes the cofactor glutathione, diminished fractional vitamin C generation (0.1 vs 0.03, p=0.0009). Elevation in tumor lactate generation was seen in untreated (125.1±17.6µM, p=0.005) and radiated mice (149.4±32.6µM, p=0.01). Treatment with radiation generated higher vitamin C concentrations in tumors relative to contralateral brain (46.8±4.8µM, p=0.002). Radiated tumors were distinguished by higher ratio of lactate to vitamin C compared to untreated tumor controls (3.7 vs 2.5, p=0.07), and the same relationship was preserved between treated and untreated non-tumor brain. CONCLUSION The ratio of vitamin C/lactate detects the metabolic effects of radiation in brain tumors, inspiring its’ potential as a biomarker for treatment response. To further characterize these findings, examination of survival and modulation of radiosensitivity are ongoing.