Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation

The partial pressure of oxygen (pO2) and pH play critical roles in tumor biology and therapy. We report here the first combined, high-resolution (< or = 10 microns) measurements of interstitial pH and pO2 profiles between adjacent vessels in a human tumor xenograft, using fluorescence ratio imagi...

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Bibliographic Details
Published inNature medicine Vol. 3; no. 2; p. 177
Main Authors Helmlinger, G, Yuan, F, Dellian, M, Jain, R K
Format Journal Article
LanguageEnglish
Published United States 01.02.1997
Subjects
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Animals
Colonic Neoplasms - metabolism
Colonic Neoplasms - pathology
Humans
Hydrogen-Ion Concentration
Mice
Microscopy, Fluorescence
Neoplasm Transplantation
Neoplasms, Experimental - metabolism
Neoplasms, Experimental - pathology
Oxygen - metabolism
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Summary:The partial pressure of oxygen (pO2) and pH play critical roles in tumor biology and therapy. We report here the first combined, high-resolution (< or = 10 microns) measurements of interstitial pH and pO2 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 pO2 profiles; (2) a discordant relation between local pH profiles and corresponding pO2 profiles, yet a strong correlation between mean pH and pO2 profiles; (3) no correlation between perivascular pH/pO2 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.
ISSN:1078-8956
1546-170X
DOI:10.1038/nm0297-177