LACTATE TURNOVER IN RAT GLIOMA MEASURED BY IN-VIVO NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY

Elevated tissue lactate concentrations typically found in tumors can b e measured by irt vivo nuclear magnetic resonance (NMR) spectroscopy. In this study, lactate turnover in rat C6 glioma was determined from i n vivo H-1 NMR measurements of [3-C-13]lactate buildup during steady-s tate hyperglycemia with [1-C-13]glucose. With this tumor model, a narr ow range of values was observed for the first-order rate constant that describes lactate efflux, k(2) = 0.043 +/- 0.007 (n = 12) SD min(-1). For individual animals, the standard error in k(2) was small (<18%), which indicated that the NMR data fit the kinetic model well. Lactate measurements before and after infusing [1-C-13]glucose showed that the majority of the tumor lactate pool was metabolically active. Signals from C-13-labeled glutamate in tumors were at least 10-fold smaller th an the [3-C-13]lactate signal, whereas spectra of the contralateral he mispheres revealed the expected labeling of [4-C-13]glutamate, as well as [2-C-13] and [3-C-13]glutamate, which indicates that label cycled through the tricarboxylic acid cycle in the brain tissue, Lack of sign ificant C-13 labeling of glutamate was consistent with low respiratory metabolism in this glioma, It is concluded that lactate in rat C6 gli oma is actively turning over and that the kinetics of lactate efflux c an be quantified noninvasively by 1H NMR detection of C-13 label. This noninvasive NMR approach may offer a valuable tool to help evaluate t umor growth and metabolic responsiveness to therapies.