Non-invasive determination of tumor oxygen tension and local variation with growth

Purpose: The objective was to develop and demonstrate a novel noninvasive technique of measuring regional pO₂ in tumors. The method is based on measuring ¹⁹F nuclear magnetic resonance spin-lattice relaxation rate (R₁ = 1 T₁) of perfluorocarbon (PFC) emulsion discretely sequestered in a tumor. Methods and Materials: We have examined pO₂ in the Dunning prostate tumor R3327-AT1 implanted in a Copenhagen rat.Oxypherol blood substitute emulsion was administered intravenously and became sequestered in tissue. Proton magnetic resonance imaging (MRI) showed tumor anatomy and correlated ¹⁹F MRI indicated the distribution of perfluorocarbon. Fluorine-19 spectroscopic relaxometry was used to measure P02 in the tumor and repeated measurements over a period of 3 weeks showed the variation in local pO₂ during tumor growth. Results: Perfluorocarbon initially resided in the vascularized peripheral region of the tumor: ¹⁹F nuclear magnetic resonance R₁ indicated pO₂ ∼ 75 torr in a small tumor (∼1 cm) in an anesthetized rat. As the tumor grew, the sequestered PFC retained its original distribution. When the tumor had doubled in size the residual PFC was predominantly in the core of the tumor and the p02 of this region was ∼-1 torr indicating central tumor hypoxia. Conclusion: We have demonstrated a novel noninvasive approach to monitoring regional tumor pO₂. Given the critical role of oxygen tension in tumor response to therapy this may provide new insight into tumor physiology, the efficacy of various therapeutic approaches, and ultimately provide a clinical technique for assessing individual tumor oxygenation.