Measuring tumor glycolytic flux in vivo using fast deuterium magnetic resonance imaging

Abstract Background Tumor cells frequently show high rates of aerobic glycolysis, which provides the glycolytic intermediates needed for the increased biosynthetic demands of rapid cell growth and proliferation. These high rates of glycolysis have enabled disease detection and treatment response monitoring using Positron Emission Tomography measurements of 2-([18F]fluoro)-2-deoxy-D-glucose uptake (FDG-PET) and 13C magnetic resonance (MR) spectroscopic imaging of hyperpolarized [1-13C]pyruvate metabolism. However, neither of these techniques can provide quantitative images of glycolytic flux from glucose to lactate. Purpose To demonstrate that fast deuterium MRI can be used for quantitative mapping of tumor glycolytic flux and to assess treatment response. Methods A fast 3D deuterium MRI pulse sequence, with a time resolution of 10 minutes, was used to image glycolytic flux in a murine tumor model following a bolus injection of D-[6,6’-2H2]glucose, before and 48 h after treatment with a chemotherapeutic agent. Tumor lactate labeling, expressed as the lactate/water and lactate/glucose signal ratios, was also assessed in localized 2H MR spectra. Statistical significance was tested with a one-sided, paired t-test. Results The deuterium MR spectroscopic images showed heterogeneity in glycolytic flux across the tumor and an early decrease in flux following treatment with a chemotherapeutic drug. Spectroscopic measurements on 5 animals showed a decrease in the lactate/water signal ratio, from 0.33 ± 0.10 to 0.089 ± 0.039 (p=.005) and in the lactate/glucose ratio, which decreased from 0.27 ± 0.12 to 0.12 ± 0.06 (p=.04), following drug treatment Conclusion Rapidly acquired deuterium MR spectroscopic images can provide quantitative and spatially resolved measurements of glycolytic flux in tumors that can be used to assess treatment response.This work was funded by Marie Curie ITN studentship (EUROPOL); Grant number: 642773 and Cancer Research UK Program Grants (17242 and 16465)