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 alpha- and beta-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.