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FSaII Mouse Tumor Metabolic Changes with Different Doses of Glucose Measured by ³¹P Nuclear Magnetic Resonance¹

Departments of Medical Physics, Medical Imaging, and Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [J. A. K.], and Department of Radiation Medicine, Edwin L. Steele Laboratory of Radiation Biology, Massachusetts General Hospital, Boston, Massachusetts 02114 [M. P. F., P. W. V., L. E. G.]

Tumor acidosis and energy deprivation enhance thermal sensitivity. We have used in vivo ³¹P nuclear magnetic resonance spectroscopy to noninvasively monitor changes in pH and energy metabolism in FSaII mouse tumors after i.p. administration of glucose. A dose of 5 g/kg glucose induced a pH drop of 0.31 units without any statistically significant change in energy status. The pH changes resolved within 2 h. In contrast, administration of 10 g/kg glucose resulted in a severe acidosis (mean nadir pH of 6.19 corresponding to a mean pH drop of 0.96 units) and loss of energy, the latter most probably being due to an acidosis-induced inhibition of glycolysis during ischemic hypoxia. The resulting acidosis and energy loss were more persistent and resolved in 5.5–28 h. In contrast, after an identical dose of mannitol (10 g/kg), a pH drop of approximately only 0.1 units over 72 min was noted. The data suggest that both cleavage of glucose to lactic acid and blood flow inhibition are involved in glucose induced tumor acidosis. In vivo ³¹P nuclear magnetic resonance spectroscopy may be useful clinically to monitor therapeutic attempts at enhancing thermal sensitivity.

¹ This investigation has been supported in part by National Cancer Institute Grants R29 CA43841 and R01-CA22860 and by The Whitaker Foundation.

² To whom requests for reprints should be addressed, at Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021.

Received 7/ 9/87. Revised 5/ 9/88. Revised 7/18/88. Accepted 7/27/88.