Measurement of tumor hypoxia by invasive and non-invasive procedures: a review of recent clinical studies.

The potential importance of hypoxic cells in cancer treatment response has been debated since their presence in human tumors was inferred by the classical studies of Thomlinson and Gray. Tumor cells which contain low concentrations of molecular oxygen display resistance to high energy photon irradiation and some chemotherapy regimens, in both in vitro and animal tumor studies. No diagnostic procedure is currently available for measuring the oxygenation status of human tumors at the time of diagnosis or throughout treatment. Recent studies with oxygen electrodes and sensitizer-adducts indicate a wide heterogeneity of oxygen levels within solid human tumors, even for tumors of similar histology and size. These studies suggest that to determine the relative importance of tumor hypoxia in treatment resistance, a "predictive assay" for monitoring tumor oxygenation status in individual patients will be required. Recently, several sophisticated techniques for measuring tumor oxygen levels and tumor metabolism have indicated both intertumor and intratumor heterogeneity of tumor oxygen levels and other metabolites. While providing useful information about human tumor biology, most of the invasive procedures are not appropriate as a standard diagnostic tool. Non-invasive measurements of 1) sensitizer-adducts by nuclear medicine procedures and 2) tumor energetics by 31P NMR spectroscopy might be developed as routine predictors of tumor oxygenation and possible treatment outcome.