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In Vitro and in Vivo ³¹P Nuclear Magnetic Resonance Measurements of Metabolic Changes Post Radiation¹

Departments of Medical Physics [U. M., A. A. A., D. B., J. A. K.], Radiology [D. B., J. A. K.], and Medicine [J. A. K.], Memorial Sloan-Kettering Cancer Center, and Cornell University Graduate School of Medical Sciences [U. M.], New York, New York 10021; The Cancer Research Institute, New York Medical College, Elmsford, New York 10523 [F. T.]; and Beth Israel Medical Center, New York, New York 10003 [A. A. A.]

Radiation-induced metabolic changes previously observed in tumors using phosphorus nuclear magnetic resonance spectroscopy include changes in the relative amounts of the phospholipid precursors phosphoethanolamine and phosphocholine, increases in membrane catabolites, and increases in energy status. To elucidate the degree to which these in vivo alterations are a result of intrinsic cellular changes versus radiation-induced systemic effects, the Radiation-Induced Fibrosarcoma-1 tumor model was studied before and over the course of 7 days after a single dose of 17 Gy. In vivo studies were performed with tumors implanted in C3H/He mice; in vitro studies used cells that were perfused in agarose gel threads after being grown, radiated, and maintained in monolayer. The statistically significant increases in the downfield component of the phosphomonoester peak, which consists primarily of phosphoethanolamine, compared to the upfield component, phosphocholine, were qualitatively similar in vivo and in vitro post radiation. Statistically significant increases in the membrane catabolite glycerophosphocholine, a phosphodiester, were also observed in both tumors and cell culture after irradiation, with a greater percentage change in vitro. This suggest that changes in the phosphomonoester and phosphodiester concentrations are primarily an intrinsic effect of radiation on cellular metabolism, modulated to a lesser degree by systemic effects. In contrast, the statistically significant increases in energy status after the 17-Gy dose showed markedly different temporal responses in the two systems. Therefore, energy status changes observed in vivo are due largely to systemic changes, such as changes in blood flow. Flow cytometry data obtained from the cultured cells showed a sustained increase in the G₂-M fraction starting at 24 h, the first time point measured after irradiation, which continued for the 7 days studied post radiation. These data indicate that the in vivo changes detected by nuclear magnetic resonance in phospholipid precursors and catabolites occur directly at the cellular level and may reflect cell death or growth inhibition after antineoplastic therapy.

¹ This work was supported by Grants 5 PO1 CA 25842-14 and NIH CA 28704. 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 9/ 9/94. Accepted 1/17/95.

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