Regional tumor oxygen dynamics: ¹⁹F PBSR EPI of hexafluorobenzene

We demonstrate a novel approach to measuring regional tumor oxygen tension using ¹⁹F pulse burst saturation recovery echo planar imaging (EPI) relaxometry of hexaflurobenzene. Hexafluorobenzene offers exceptional sensitivity to changes in oxygen tension, and has a single resonance making it ideal for imaging studies. By combining a pulse burst saturation recovery preparation sequence with EPI, the relaxation experiments were performed in ~20 min facilitating measurements of dynamic changes in pO₂ accompanying interventions. Direct intratumoral administration of hexafluorobenzene permitted labeling of specific regions of interest and imaging provided maps of pO₂, confirming distinct intra tumoral heterogeneity. For a group of three Dunning prostate adenocarcinoma R3327-AT1 tumors interrogation of the central tumor region showed skewed pO₂ distributions with considerable radiobiological hypoxia (~90% voxels had pO₂ < 15 torr) when rats breathed 33% O₂. Altering the inspired gas to pure oxygen caused distributions to shift towards increased pO₂ with significant increases in mean oxygen tension (p < 0.05) in two cases. Interrogation of both central and peripheral regions in a fourth tumor showed bimodal distribution for tumor oxygenation including ~75% voxels with pO₂ > 15 tort. EPI allows the fate of individual voxels to be traced: upon altering the inspired gas to pure oxygen those voxels with baseline pO₂ > 30 torr showed significant changes (p < 0.05), whereas those with pO₂ < 16 torr showed minimal response. The precision of the measurements, together with the ability to simultaneously examine dynamic changes in multiple regions should provide a useful technique for investigating tumor hypoxia with respect to therapy.