INVIVO C-13 NMR-SPECTROSCOPY OF GLUCOSE-METABOLISM OF RIF-1 TUMORS

An efficient method for measuring in vivo 13C NMR spectra of tumors has been developed and employed to monitor glucose metabolism in radiation‐induced fibrosarcomas (RIF‐1) subcutaneously implanted in C3H/HeN mice. [1‐13C]Glucose was injected directly into the tumors at a dose of 1 g/kg body wt. Spectra were obtained with a Bruker AM 360‐WB spectrometer (8.4 T/8.9 cm bore) employing a homebuilt probe equipped with a four‐turn solenoidal coil (1.5 cm outer diameter) for detection of 13C signals and a Helmholtz coil (two 3‐cm turns separated by a 3‐cm gap, oriented orthogonally to the 13C coil) for 1H decoupling. In addition to the natural abundance 13C resonances of the tumors, signals were detected from the α‐and β‐anomers of labeled glucose. Within 15 min following injection of labeled glucose [3‐13C]lactate and [3‐13C]alanine were detected. Lactate labeling approached steady state levels within about 50 min after glucose injection; in contrast, alanine labeling increased continuously over the duration of the experiment (70 min). Sixty minutes after glucose injection, the ratio of the intensity of [3‐ 13C]lactate to the principal lipid methylene resonance (30 ppm from external tetramethylsilane), which served as an internal intensity reference, was correlated with tumor size, whereas the corresponding ratio of the [3‐ 13C] alanine resonance was not. Labeling of glutamate was below the level of detection in the in vivo spectra; however, labeling of C4‐glutamate at a level approximately 50‐fold lower than the level of [3‐ 13C]lactate was detected in perchloric acid extracts. Incorporation of 13C label into C2‐and C3‐glutamate and C2‐lactate was also observed. © 1991 Academic Press, Inc. Copyright © 1991 Wiley‐Liss, Inc., A Wiley Company