Regional tumor oxygen tension: Fluorine echo planar imaging of hexafluorobenzene reveals heterogeneity of dynamics

Purpose: Therapeutic success could be enhanced if therapy were tailored to the characteristics of specific tumors. We have been developing novel approaches to measuring tumor oxygen tension in vivo, and recently reported a method based on ¹⁹F nuclear magnetic resonance (NMR) spin lattice echo planar imaging (EPI) relaxometry of hexafluorobenzene (HFB). We have now examined the feasibility of monitoring dynamic changes in regional tumor oxygenation in response to respiratory challenge. Preliminary data in one tumor show distinct differences before and subsequent to irradiation. Methods and Materials: Dunning prostate adenocarcinoma R3327-AT1 was grown in the form of pedicles on the foreback of male Copenhagen rats. When the tumors reached ~ 1 cm diameter, HFB (40 μl) was administered by direct intratumoral injection deliberately dispersed to interrogate both central and peripheral regions. Local pO₂ was determined using pulse burst saturation recovery ¹⁹F NMR EPI on the basis of the spin lattice relaxation rate. Results: Interrogation of both central and peripheral regions of tumors showed bimodal distribution for oxygenation, including many voxels with pO₂ < 15 torr. Altering the inspired gas to 100% O₂ produced significant elevation for regions with initially high pO₂ (p < 0.01), but the temporal course of dynamic changes varied for each voxel. Many voxels with low pO₂ showed little response. Following irradiation (20 Gy), tumor oxygenation was significantly elevated and remained high for at least 10h. Conclusion: We believe this method provides a valuable new approach to investigate tumor oximetry that may extend our understanding of tumor physiology, and could have prognostic value.