Tracking the Metabolic Fates of $^{\mathrm{13}}$C and $^{\mathrm{15}}$N-alanine in Glioblastoma

Glioblastoma is one of the most lethal forms of cancer with a very dismal survival rate. Such tumors are mostly chemoresistant and difficult to detect at an early stage. Thus, there is an unmet clinical need of non-invasive methods for early detection of glioblastoma. In this study, we have investigated the metabolism of $^{\mathrm{13}}$C,$^{\mathrm{15}}$N-labeled alanine in SfXL glioblastoma cells with different incubation times of the substrate using NMR spectroscopy. Our data show high production of $^{\mathrm{13}}$C-lactate from $^{\mathrm{13}}$C-alanine and that the intermediate metabolite $^{\mathrm{13}}$C-pyruvate was not visible in the $^{\mathrm{13}}$C NMR spectra up to 48 hours of incubation time. Consequently, we also track the metabolic fate of $^{\mathrm{15}}$N-amino arm of alanine to complete the metabolic story of this amino acid in cancer. These results suggest that glioblastoma cells prefer rapid lactic acid production from alanine-derived pyruvate, indicative of the hyperactive ALT and LDH activities in these cells. This study is supported by Welch grant AT-1877-20180324, DOD grants W18XWH-17-1-0303 and DOD W81XWH-19-1-0741, CPRIT grant RP180716, and the UTD Collaborative Biomedical Research Award (CoBRA).