PATHOPHYSIOLOGICAL APPROACHES TO IDENTIFYING TUMOR HYPOXIA IN PATIENTS

The present report summarizes observations of the authors on tumor oxygenation and on techniques for characterizing tumor hypoxia in patients. Cryospectrophotometric measurements of HbO2 saturations in tumor microvessels allow for estimates of the proportion of well oxygenated tissue regions. Labeling of tissue areas at oxygen (O2) tensions (pO2) < 10 mm Hg with misonidazole may be used for a general characterization of the oxygenation status in patient tumors rather than for the determination of the radiobiologically hypoxic cell fraction. Quantitative bioluminescence and single photon imaging make it possible to determine ATP concentrations in absolute terms with a spatial resolution at the cellular level. It is shown that the ATP distribution reflects the efficiency of the O2 supply to tumors. Since all these techniques rely on biopsy material, the measured values can be assessed in relation to the histological structure and vascular pattern of tumors. Such a direct interrelationship is not obtained when using polarographic microelectrodes in tumor tissue. However, a novel technology, the "computerized pO2 histography" has enabled direct polarographic measurements of pO2 values in patients, in extended and systematic clinical trials. Preliminary results in cervix and breast cancers demonstrate that pO2 values are lower in tumors than in adjacent normal tissues, and that great intra- and intertumoral differences occur even among tumors of the same clinical stages and histological grades, illustrating the necessity of such a pathophysiological approach to an "individualization" of tumor therapy.