Interstitial pH and pO(2) gradients in solid tumors in vivo: High-resolution measurements reveal a lack of correlation

The partial pressure of oxygen (pO(2)) and pH play critical roles in tumor biology and therapy. We report here the first combined, high-resolution (less than or equal to 10 mu m) measurements of interstitial pH and pO(2) profiles between adjacent vessels in a human tumor xenograft, using fluorescence ratio imaging and phosphorescence quenching microscopy. We found (1) heterogeneity in shapes of pH and pO(2) profiles; (2) a discordant relation between local pH profiles and corresponding pO(2) profiles, yet a strong correlation between mean pH and pO(2) profiles; (3) no correlation between perivascular pH/pO(2) and nearest vessel blood flow; and (4) well-perfused tumor vessels that were hypoxic and, consequently, large hypoxic areas in the surrounding interstitium. Such multiparameter measurements of the in vivo microenvironment provide unique insights into biological processes in tumors and their response to treatment.