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Lactate Turnover in Rat Glioma Measured by in Vivo Nuclear Magnetic Resonance Spectroscopy¹

Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Elevated tissue lactate concentrations typically found in tumors can be measured by in vivo nuclear magnetic resonance (NMR) spectroscopy. In this study, lactate turnover in rat C6 glioma was determined from in vivo ¹H NMR measurements of [3-¹³C]lactate buildup during steady-state hyperglycemia with [1-¹³C]glucose. With this tumor model, a narrow range of values was observed for the first-order rate constant that describes lactate efflux, k₂ = 0.043 ± 0.007 (n = 12) SD min^-1. For individual animals, the standard error in k₂ was small (<18%), which indicated that the NMR data fit the kinetic model well. Lactate measurements before and after infusing [1-¹³C]glucose showed that the majority of the tumor lactate pool was metabolically active. Signals from ¹³C-labeled glutamate in tumors were at least 10-fold smaller than the [3-¹³C]lactate signal, whereas spectra of the contralateral hemispheres revealed the expected labeling of [4-¹³C]glutamate, as well as [2-¹³C] and [3-¹³C]glutamate, which indicates that label cycled through the tricarboxylic acid cycle in the brain tissue. Lack of significant ¹³C labeling of glutamate was consistent with low respiratory metabolism in this glioma. It is concluded that lactate in rat C6 glioma is actively turning over and that the kinetics of lactate efflux can be quantified noninvasively by ¹H NMR detection of ¹³C label. This noninvasive NMR approach may offer a valuable tool to help evaluate tumor growth and metabolic responsiveness to therapies.

¹ This research was supported by NIH Grants CA64338 and RR08079 and the W. M. Keck foundation.

² To whom requests for reprints should be addressed, at Center for Magnetic Resonance Research, 2021 6th Street Southeast, Minneapolis, MN 55455. Phone: (612) 626-2001; Fax: (612) 626-2004; E-mail: gar@cmrr.umn.edu.

Received 6/17/98. Accepted 9/17/98.

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