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Changes in Radiation Sensitization Induced by Fluosol-DA as Measured by ³¹P Nuclear Magnetic Resonance Spectroscopy¹

Departments of Medical Physics [J. A. K., A. A. A., M. L. D., D. B.], Medical Imaging [J. A. K.], Medicine [J. A. K.], and Psychiatry [A. B. K.], Memorial Sloan-Kettering Cancer Center New York, New York 10021; The Rockefeller University [D. C.] New York, New York 10021; and Department of Radiation Oncology, Henry Ford Hospital [J. H. K.], Detroit, Michigan 48202

Numerous agents have been studied in attempts to sensitize radioresistant hypoxic tumor cells. We have investigated the effect of Fluosol-DA plus carbogen (95% oxygen and 5% CO₂) on the sensitivity of a radioresistant mammary carcinoma in C₃H/He mice and also on tumor metabolism by ³¹P nuclear magnetic resonance spectroscopy. Statistically significant increases in phosphocreatine/P_i were noted for small- (150–350 mm³) and medium-(351–650 mm³) sized tumors treated with Fluosol-DA plus carbogen. Small tumors were shown to undergo significant radiosensitization in the presence of Fluosol-DA plus carbogen and medium-sized tumors showed a lesser degree of radiosensitization. Large tumors (>900 mm³) showed no effect. Fluosol-DA or carbogen alone had no effects on animals with any tumor volume, as monitored by significant changes in radiosensitivity or nuclear magnetic resonance parameters. An approximately linear relationship was found between the decrease in the values for radiation dose which yields 50% tumor control and the increase in phosphocreatine/P_i, with a correlation of r = -0.93. ³¹P nuclear magnetic resonance spectroscopy may be useful for monitoring changes in radiosensitivity induced by agents which alter tumor oxygenation and subsequent metabolic status.

¹ This work was supported by National Cancer Institute Grant R29 CA 43841 and funds from the Whitaker Foundation.

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 4/30/90. Accepted 8/20/90.

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