Imaging a hallmark of cancer: hyperpolarized [U-2H, U-13C]-glucose and hyperpolarized [1-13C]-dehydroascorbic acid can monitor TERT expression in gliomas

Expression of telomerase reverse transcriptase (TERT) is a fundamental hallmark of cancer. Identification of imaging biomarkers of TERT expression will facilitate non-invasive assessment of tumor burden and response to therapy. Our studies in glioma indicate that TERT expression leads to increased redox capacity characterized by elevated ¹H-MRS-detectable glutathione and NADPH. Concomitantly, TERT increases ¹³C-MRS-detectable flux of glucose through the pentose phosphate pathway, which provides NADPH. Importantly, hyperpolarized [U-²H, U-¹³C]-glucose and hyperpolarized [1-¹³C]-dehydroascorbic acid can image these alterations in glucose and redox metabolism. Our study identifies potential non-invasive translational metabolic imaging probes of TERT expression in glioma and possibly other cancers.