Assessment of changes in murine tumor oxygenation in response to nicotinamide using 19F NMR relaxometry of a perfluorocarbon emulsion

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Abstract
The oxygen dependencies of the 19F NMR spin-lattice relaxation rates (R1 = 1/T1) of a perfluorocarbon emulsion sequestered in a murine tumor model has been used to evaluate nicotinamide, a radiosensitizer believed to act through enhanced tissue oxygenation. Fluorine-19 NMR spectroscopic measurements from solid Radiation-Induced Fibrosarcoma (RIF-1) tumors in C3H mice showed a statistically significant improvement in tumor pO2 for a Nicotinamide-treated group, with a ΔpO2 = 4.7 ± 3 torr (=mm Hg) (Mean ± SEM) at t = 60 min (P <.01), and 4.5 ± 3 at t = 70 min post intraperitoneal injection (P < 0.02) as compared with saline-treated Controls, while several other time points for which t > 30 min were significant at the P < 0.05 level. Both groups had n = 10, and the statistics were based on Student's one-tailed group t test. By comparison, in another study group where breathing gas was switched from air to 100% O2, a statistically insignificant increase of 2 torr was realized in tumor pO2 (n = 9). The maximal treatment effect occurs at a delay of 60 to 70 min, consistent with results obtained by other investigators using radiobiology techniques. Fluorine-19 spectroscopic relaxometry can measure therapeutically meaningful changes in in vivo tumor pO2 and represents an improvement in expenditures of time, animal resources, and statistical power over conventional radiobiological methods.