Oxygent. A novel probe of tissue oxygen tension

There is developing interest in the use of fluorinated materials to act as physiological reporter molecules in vivo. Perfluorocarbon emulsion blood substitutes exhibit intense ¹⁹F nuclear magnetic resonance (NMR) signals, which are sensitive to the microenvironmental milieu. In particular, the NMR spin-lattice relaxation rates (R₁) of the ¹⁹F resonances of perfluorocarbon emulsions are sensitive to oxygen tension and temperature. We have previously exploited this phenomenon to measure dynamic changes in pO₂ in the tumor and liver of live mice and the perfused rat heart using Oxypherol (an emulsion of perfluorotributylamine (pftb), Alpha Therapeutics). We have now examined the use of Oxygent (an emulsion of perfluorooctylbromide (PFOB), Alliance Pharmaceuticals) as a probe of oxygen tension. The ¹⁹F NMR spectrum of PFOB has 7 well-resolved signals at 7 Tesla. Each shows a linear relationship between R₁ and pO₂. Preliminary data indicate that Oxygent is considerably more sensitive to changes in pO₂. At 37 C the most sensitive resonance in PFOB shows a relationship R₁ (s^-1) = 0.31 + 1.82 × 10^-2 %pO₂. This compares with R₁ (s^-1) = 0.88 + 1.72 × 10^-2 %pO₂ for pftb. The enhanced sensitivity should facilitate more accurate monitoring of small radiobiologically significant changes in pO₂ in tumors. Given the preliminary use of PFOB in clinical trials, this may form a basis for monitoring oxygen tension in patients in the near future. We have previously shown that the alternate PFC emulsion Fluosol (Alpha Therapeutics) was readily detected by NMR at 2 Tesla in a patient following radio-therapy. It is known that PFOB accumulates in the reticuloendothelial system and in tumors, and we are currently evaluating the biodistribution and tissue retention of Oxygent to assess the utility of this emulsion in vivo as a probe of oxygen tension.