Evaluation of tumor energy metabolism and microvascular blood flow after glucose or mannitol administration using 31P nuclear magnetic resonance spectroscopy and laser Doppler flowmetry.
The effects of intraperitoneally administered glucose or mannitol (5 mg/g body weight, 25% solutions) on tumor energy metabolism and tumor red blood cell flux were studied using 31P-nuclear magnetic resonance spectroscopy and laser Doppler flowmetry. Isotransplants of a spontaneous murine fibrosarcoma growing in the hind foot dorsum were used. 31P-nuclear magnetic resonance and laser Doppler flowmetry studies in glucose treated animals were performed on small (congruent to 100 mm3) and large (congruent to 300 mm3) tumors. In mannitol treated animals, tumors with an average volume of congruent to 200 mm3 were used. Using this tumor model, intraperitoneally administration of the hypertonic sugar solutions caused similar declines in tumor microcirculation (mannitol, 60 +/- 8% flow reduction; glucose, 72 +/- 4% flow reduction; t = 60 min). These changes were not glucose-specific and can primarily be explained by a water shift into the abdominal cavity and an associated hypovolemic hemoconcentration. A stable (small tumors) or transiently increased (large tumors) tumor energy metabolism which occurred after glucose administration was probably caused by a transiently increased glucose availability. The decline in energy metabolism after mannitol, a non-metabolized sugar alcohol, and the earlier decline in tumor pH seen in the glucose treated animals, supports this conclusion. The differences in the high energy phosphate response to glucose seen in small compared with large tumors, suggests that the baseline metabolic state of larger tumors includes a glucose deficiency in addition to tumor hypoxia.
Okunieff
P
P
Massachusetts General Hospital, Harvard Medical School, Dept. of Radiation Medicine, Boston 02114.
Vaupel
P
P
Sedlacek
R
R
Neuringer
L J
LJ
D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007834:Lasers; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D008833:Microcirculation / Q000187:drug effects*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism*
D008353:Mannitol; D005947:Glucose