In vivo 13CNMR 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 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.
Department of Radiology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
I
I
Constantinidis
J C
JC
Chatham
J P
JP
Wehrle
J D
JD
Glickson
D000818:Animals; D002244:Carbon; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D015552:Injections, Intralesional; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007773:Lactates / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D007773:Lactates; D002244:Carbon; D005947:Glucose