TMET-52. Proof of concept stable isotope tracing study: defining the metabolomic profile of meningiomas through evaluation of dura vs core tissue utilization and uptake of heavy labeled glucose

Abstract BACKGROUND Stable isotope tracing is a novel way to directly interrogate metabolic pathways by tracking substrates that contain a heavy isotope, such as 13C. Recent work by our group (Scott et al 2023) utilized this technique to interrogate glioblastoma cells compared to normal cortex. This work found that, compared to normal cortex, glioblastoma cells preferentially use glucose to make nucleotides. There has never been a study to capitalize on this unique strategy for interrogating the metabolomic profile of meningiomas, despite it being the most common primary intracranial lesion. Therefore, we utilized an untargeted analysis to evaluate the metabolic differences between dura and core enhancing meningioma tissue. METHODS A patient meningioma sample was obtained as a part of the Human Isotope Tracing Program. Tissue from the enhancing core and the dura were collected. The tissue was flash frozen, homogenized, and prepped for liquid chromatography mass spectrometry. The data were extracted with skyline and corrected for the natural isotope abundance with IsoCoroecter software. RESULTS There was uptake of the heavy labeled glucose in both dura and the enhancing core. However, differential utilization of the glucose was appreciated. Compared to the dura, the enhancing core was found to have a higher abundance of labeling in amino acids, most notably in glutamate, glutamine and aspartate. There were also higher levels of labeling in core tissue from metabolites in glycolysis and the tricyclic acid cycle as compared to the dura. CONCLUSIONS These results demonstrate that evaluating the metabolic profile of meningiomas through stable isotope tracing is feasible and provides intriguing information regarding the differences in dura and core tumor metabolism. Core enhancing tissue from meningiomas has a higher utilization of the glycolysis and tricyclic acid cycles as compared to the dura. Understanding these differences can be utilized to create novel therapeutics and decrease morbidity and mortality for these patients.