Tumor oxygen dynamics with respect to growth and respiratory challenge: investigation of the Dunning prostate...

We recently described a novel approach to measuring regional tumor oxygen tension using (19)F nuclear magnetic resonance echo planar imaging relaxometry (FREDOM) of hexafluorobenzene. We have now applied this technique to evaluate in detail the oxygen tension dynamics in the relatively slowly growing, moderately well-differentiated Dunning prostate R3327 HI rat tumor with respect to tumor growth and respiratory challenge. Seven individual tumors were assessed repeatedly over a period of 5 weeks ( approximately 4 volume doubling times). For small tumors (<1 cm(3)), the mean pO(2) ranged from 28 to 44 Torr under baseline conditions, decreasing to less than 10 Torr when the tumors reached 5 to 6 cm(3), with a strong inverse correlation between the baseline tumor oxygen tension and the tumor size. The hypoxic fraction (defined as the percentage of the voxels with pO(2) <10 Torr) increased significantly with tumor growth. Administration of oxygen or carbogen produced a significant increase (P < 0.0001) in tumor oxygenation at all stages of tumor growth. Most interestingly, even regions of these tumors that were initially poorly oxygenated responded rapidly, and significantly, to respiratory intervention, in contrast to the behavior of the faster-growing rat prostate tumors investigated previously.