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Radiation Dose-dependent Changes in Tumor Metabolism Measured by ³¹P Nuclear Magnetic Resonance Spectroscopy¹

Departments of Medical Physics [U. M., A. A. A., J. A. K.], Epidemiology and Biostatistics [H. T.], Radiology [J. A. K.], and Medicine [J. A. K.], Memorial Sloan Kettering Cancer Center, New York, New York 10021; Cornell University Graduate School of Medical Sciences, New York, New York 10021 [U. M.]; and The Rockefeller University, New York, New York 10021 [D. C.]

The effects of radiation dose upon a hypoxic murine mammary carcinoma were followed using ³¹P nuclear magnetic resonance spectroscopy. Animals were studied before and over the course of 9 days after tumors were irradiated with a single dose of 0, 4, 8, or 17 Gy. The current data is compared to our previous studies of the effects of 32 or 65 Gy on the same tumor model. The energy status of the tumors, as reflected in nucleotide triphosphate:Pi and phosphocreatine:Pi ratios, improved after receiving a dose of 8 to 65 Gy and decreased after receiving 0 or 4 Gy doses. The energy status of the 8- to 65-Gy dose cohorts reached a maximum between 1 and 4 days after irradiation. Additionally, the change in the hypoxic cell fraction 48 h after a 17-Gy dose was determined; it was calculated from changes in the doses required to control 50% of the tumors post radiation for clamped (hypoxic) and unclamped (normoxic) tumors in parallel animal cohorts. A significant decrease compared to preirradiation values was observed in the hypoxic cell fraction following 17 Gy irradiation. This decrease was temporally coincident with increases in tumor energy status measured using nuclear magnetic resonance and was similar to our previously reported results of the change in hypoxic fraction 48 h after a 32-Gy dose. Changes in the relative ratio of phosphomonoesters showed a strong dose dependence after irradiation. The downfield component of the phosphomonoester peak, which consists largely of phosphoethanolamine, increased relative to the upfield component, phosphocholine. This dose-dependent ratio reached a maximum approximately 7 days post radiation. Changes in the levels of membrane phospholipid precursors may be related to alterations in cell proliferation or may be a result of radiation-induced membrane damage.

¹ This work supported by Grant 5 PO1 CA 25842-14. U. M. is supported by the Lee Friedman Memorial Fellowship.

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

Received 4/ 6/94. Accepted 7/12/94.

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