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Quantitative Changes in Tumor Metabolism, Partial Pressure of Oxygen, and Radiobiological Oxygenation Status Postradiation¹

Departments of Medical Physics [J. A. K., A. A. A., M. L. D., U. M.], Radiology [J. A. K.], Medicine [J. A. K.], Psychiatry [A. B. K.], and Radiation Oncology [T. E. M.], Memorial Sloan Kettering Cancer Center, New York, New York 10021; Department of Radiation Oncology [J. G. R.], University of Maryland, Baltimore, Maryland 21201; and the Rockefeller University [D. C.], New York, New York 10021

Hypoxia is considered to be a major cause of tumor radioresistance. Reoxygenation of previously hypoxic areas after a priming dose of radiation is associated with an increase in tumor radiosensitivity. In a study of a hypoxic mammary carcinoma, ³¹P nuclear magnetic resonance spectra showed statistically significant increases in metabolite ratios (phosphocreatine/P_i and nucleotide triphosphate/P_i) after 65 and 32 Gy. The maximum changes in metabolite ratios after 32 Gy occurred at 48 h, although significant changes were detected at 24 h. A corresponding increase in the mean tumor pO₂ (polarographic microelectrode measurements) and a decrease in hypoxic cell fraction [changes in paired (clamped versus unclamped) tumor control dose for 50% of tumors] were also shown to occur 48 h after a priming dose of 32 Gy. A significant increase in the mean tumor pO₂, phosphocreatine/P_i, and nucleotide triphosphate/P_i, compared to initial values, was noted at 24, 48, and 96 h post 65-Gy radiation. An increase in the downfield component of the phosphomonoester peak relative to the upfield component (phosphoethanolamine), is also noted after doses of 65 and 32 Gy. These are likely to be due to cell kill and/or decreased cell proliferation. In this tumor model, ³¹P nuclear magnetic resonance spectroscopic changes postradiation are temporally coincident with and may be indicative of tumor reoxygenation as measured by the tumor control dose for 50% of tumors and oxygen-sensitive microelectrodes.

¹ This work was supported by R29 CA43841 and R01 CA44056. U.M. is supported by a Lee Friedman Memorial Fellowship.

² To whom requests for reprints should be addressed, at Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

Received 12/20/91. Accepted 6/22/92.

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