Carbohydrate metabolism of the rat C6 glioma. An in vivo 13C and in vitro 1H magnetic resonance spectroscopy study

Surface coil 13C nuclear magnetic resonance (NMR) spectroscopy was used to investigate the in vivo carbohydrate metabolism of rat C6 gliomas during and after infusion with 1-13C] glucose. In vivo 1H-decoupled 13C NMR spectra of the glioma following infusion with 1-13C]glucose revealed the direct production of 3-13C]lactic acid, 1-13C]glycogen, and 4-13C], 3-13C], and 2-13C]glutamate/glutamine. Lactate levels of in vivo gliomas increased and reached steady state levels during 1-13C]glucose infusion, and decreased following termination of infusion. Complementary in vitro studies using supernatant media collected from C6 glioma cells incubated with media containing 1-13C] or 6-13C]glucose and glutamine were examined by 1H NMR spectroscopy. The 3-(13C/12C)]lactate ratios obtained from 1H spectra of supernatant media containing 1-13C]glucose revealed the percentage of glucose metabolized through the hexose monophosphate shunt to be 10.01 +/- 0.85% (n = 3), while similar measurements of media containing 6-13C]glucose and glutamine showed that glutaminolysis contributed 9.0 +/- 1.0% of total lactate production under these conditions. Enzymatic analysis of media determined lactate production to be 139 +/- 9 nmol per 10(6) cells per h (n = 4). These measurements demonstrate the ability of NMR to monitor brain tumor carbohydrate metabolism both in vitro and in vivo.