Measurement of tumor oxygenation.

There is now clear evidence that the oxygenation status of cells in tumours can influence the response of those tumours to therapy. The classic example is for radiation, to which oxygen deficient hypoxic cells are more resistant than cells under well oxygenated conditions (1). Most solid animal tumours have been shown to contain such resistant cells in different proportions (2) and it is a major factor that influences the overall response of the tumour to radiation. There is even evidence from clinical studies indicating the presence of such cells in certain types of human tumours, and that by eliminating these cells significant improvements in radiation response can be obtained (3). Tumour oxygenation status has also been shown to be an important factor in the response of tumours to certain chemotherapeutic agents, cytokines, hyperthermia, and photodynamic therapy (4). More recent studies are now providing evidence that tumour oxygenation, especially hypoxia, may also influence malignant progression through effects on signal transduction pathways and the regulation and transcription of various genes (5, 6). It naturally follows that if one could accurately measure the oxygenation status of individual tumours one should be able to better predict treatment outcome and select appropriate therapies to improve it. In this review we will define the parameters of interest, discuss the most clinically applicable methods for measuring these parameters, and make some suggestions as to how future studies in this area should proceed.

[1]  H. Awwad,et al.  Intercapillary distance measurement as an indicator of hypoxia in carcinoma of the cervix uteri. , 1986, International journal of radiation oncology, biology, physics.

[2]  M. Dewhirst,et al.  Perivascular oxygen tensions in a transplantable mammary tumor growing in a dorsal flap window chamber. , 1992, Radiation research.

[3]  S. Rockwell,et al.  Hypoxic fractions of solid tumors: experimental techniques, methods of analysis, and a survey of existing data. , 1984, International journal of radiation oncology, biology, physics.

[4]  M. Dewhirst,et al.  Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma. , 1996, Cancer research.

[5]  Raleigh,et al.  Measuring Tumor Hypoxia. , 1996, Seminars in radiation oncology.

[6]  M. Horsman Hypoxia in Tumours: Its Relevance, Identification, and Modification , 1993 .

[7]  P Vaupel,et al.  Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. , 1996, Cancer research.

[8]  L. H. Gray,et al.  The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. , 1953, The British journal of radiology.

[9]  M. Dewhirst,et al.  Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. , 1997, International journal of radiation oncology, biology, physics.

[10]  S. Rockwell Use of a perfluorochemical emulsion to improve oxygenation in a solid tumor. , 1985, International journal of radiation oncology, biology, physics.

[11]  M. Dewhirst,et al.  Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. , 1996, Cancer research.

[12]  Rakesh K. Jain,et al.  Interstitial pH and pO2 gradients in solid tumors in vivo: High-resolution measurements reveal a lack of correlation , 1997, Nature Medicine.

[13]  P. Okunieff,et al.  Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. , 1989, Cancer research.

[14]  P Kolstad,et al.  Intercapillary distance, oxygen tension and local recurrence in cervix cancer. , 1968, Scandinavian journal of clinical and laboratory investigation. Supplementum.

[15]  L. Révész,et al.  Variation of vascular density within and between tumors of the uterine cervix and its predictive value for radiotherapy. , 1989, International journal of radiation oncology, biology, physics.

[16]  J. Overgaard,et al.  Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. , 1996, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[17]  P. Olive,et al.  The comet assay: a comprehensive review. , 1995, Mutation research.

[18]  R. Gatenby,et al.  Oxygen distribution in squamous cell carcinoma metastases and its relationship to outcome of radiation therapy. , 1988, International journal of radiation oncology, biology, physics.

[19]  C. Grau,et al.  Detection of hypoxic cells in a C3H mouse mammary carcinoma using the comet assay. , 1997, British Journal of Cancer.

[20]  Sutherland,et al.  Tumor Hypoxia and Heterogeneity: Challenges and Opportunities for the Future. , 1996, Seminars in radiation oncology.

[21]  T K Lewellen,et al.  Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. , 1996, International journal of radiation oncology, biology, physics.

[22]  L. H. Gray,et al.  The Histological Structure of Some Human Lung Cancers and the Possible Implications for Radiotherapy , 1955, British Journal of Cancer.

[23]  M. Parliament,et al.  Measurement of hypoxia in human tumours by non-invasive spect imaging of iodoazomycin arabinoside. , 1996, The British journal of cancer. Supplement.

[24]  S. Skates,et al.  A morphometric study of the vascularity of oral squamous cell carcinomas and its relation to outcome of radiation therapy. , 1989, European journal of cancer & clinical oncology.

[25]  J. Overgaard,et al.  Modification of Hypoxia-Induced Radioresistance in Tumors by the Use of Oxygen and Sensitizers. , 1996, Seminars in radiation oncology.

[26]  J M Brown,et al.  Evidence for acutely hypoxic cells in mouse tumours, and a possible mechanism of reoxygenation. , 1979, The British journal of radiology.

[27]  I. Olivotto,et al.  Gel electrophoresis of individual cells to quantify hypoxic fraction in human breast cancers. , 1993, Cancer research.

[28]  P. Workman,et al.  Direct measurement of pO2 distribution and bioreductive enzymes in human malignant brain tumors. , 1994, International journal of radiation oncology, biology, physics.

[29]  A. Giaccia,et al.  Hypoxic Stress Proteins: Survival of the Fittest. , 1996, Seminars in radiation oncology.

[30]  D. Chaplin,et al.  Intermittent blood flow in a murine tumor: radiobiological effects. , 1987, Cancer research.

[31]  S. A. Roberts,et al.  The independence of intrinsic radiosensitivity as a prognostic factor for patient response to radiotherapy of carcinoma of the cervix. , 1997, British Journal of Cancer.