Novel 1H NMR approach to quantitative tissue oximetry using hexamethyldisiloxane

19F NMR spin-lattice relaxometry of hexafluorobenzene (HFB) has been shown to be a highly sensitive indicator of tumor oxygenation. In this study hexamethyldisiloxane (HMDSO) was identified as a proton NMR analog, and its potential as a probe for investigating dynamic changes in tissue oxygen tension (pO2) was evaluated. HMDSO has a single proton resonance (delta= -0.3 ppm) and the spin-lattice relaxation rate, Rl (= 1/T1) exhibits a linear dependence on pO2: R1 (s(-1)) = 0.1126 + 0.0013* pO2 (torr) at 37 degrees C. To demonstrate application in vivo, HMDSO was administered into healthy rat thigh muscle (100 microl) and tumors (50 microl). Local pO2 was determined by using pulse-burst saturation recovery (PBSR) 1H NMR spectroscopy to assess R1. Water and fat signals were effectively suppressed by frequency-selective excitation of the HMDSO resonance. Rat thigh muscle had a mean baseline pO2 of 35 +/- 11 torr, with a typical stability of +/-3 torr over 20 min, when the rats breathed air. Altering the inhaled gas to oxygen produced a significant increase in pO2 to 100-200 torr. In tumors, altering the inspired gas also produced significant (albeit generally smaller) changes. This new pO2 reporter molecule offers a potentially valuable new tool for investigating pO2 in vivo.