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 t umor biology and therapy. We report here the first combined, high-reso lution (less than or equal to 10 mu m) measurements of interstitial pH and pO(2) profiles between adjacent vessels in a human tumor xenograf t, using fluorescence ratio imaging and phosphorescence quenching micr oscopy. 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) pr ofiles; (3) no correlation between perivascular pH/pO(2) and nearest v essel blood flow; and (4) well-perfused tumor vessels that were hypoxi c and, consequently, large hypoxic areas in the surrounding interstiti um. Such multiparameter measurements of the in vivo microenvironment p rovide unique insights into biological processes in tumors and their r esponse to treatment.