Advertisement

Hypoxia as a Biomarker and for Personalized Radiation Oncology

  • Dirk VordermarkEmail author
  • Michael R. Horsman
Chapter
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 198)

Abstract

Tumor hypoxia is a clinically relevant cause of radiation resistance. Direct measurements of tumor oxygenation have been performed predominantly with the Eppendorf histograph and these have defined the reduced prognosis after radiotherapy in poorly oxygenated tumors, especially head-and-neck cancer, cervix cancer and sarcoma. Exogenous markers have been used for immunohistochemical detection of hypoxic tumor areas (pimonidazole) or for positron-emission tomography (PET) imaging (misonidazole). Overexpression of hypoxia-related proteins such as hypoxia-inducible factor-1α (HIF-1α) has also been linked to poor prognosis after radiotherapy and such proteins are considered as potential endogenous hypoxia markers.

Keywords

Tumor hypoxia Tumor oxygenation Pimonidazole Hypoxia-inducible factor-1α 

Notes

Acknowledgements

The authors would like to thank the following organizations for financial support: the Danish Agency for Science Technology and Innovation; the Danish Cancer Society; the EC FP7 project METOXIA (project no. 222741); the German Research Foundation (Deutsche Forschungsgemeinschaft); the Wilhelm Sander Foundation and CIRRO—the Lundbeck Foundation Center for Interventional Research in Radiation Oncology and the Danish Council for Strategic Research.

References

  1. Adams GE, Cooke MS (1969) Electron–affinic sensitization. I. A structural basis for chemical radiosensitizers in bacteria. Int J Radiat Biol 15:457–471Google Scholar
  2. Aebersold DM, Burri P, Beer KT et al (2001) Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer. Cancer Res 61:2911–2916PubMedGoogle Scholar
  3. Andersen EKF, Hole KH, Lund KV et al (2012) Dynamic contrast-enhanced MRI of cervical cancers: temporal percentile screening of contrast enhancement identifies parameters for prediction of chemoradioresistance. Int J Radiat Oncol Biol Phys 82:485–492CrossRefGoogle Scholar
  4. Bache M, Kappler M, Said HM et al (2008) Detection and specific targeting of hypoxic regions within solid tumors: current preclinical and clinical strategies. Curr Med Chem 15:322–338PubMedCrossRefGoogle Scholar
  5. Bachtiary B, Schindl M, Potter R et al (2003) Overexpression of hypoxia-inducible factor 1alpha indicates diminished response to radiotherapy and unfavorable prognosis in patients receiving radical radiotherapy for cervical cancer. Clin Cancer Res 9:2234–2240PubMedGoogle Scholar
  6. Beasley NJ, Wykoff CC, Watson PH et al (2001) Carbonic anhydrase IX, an endogenous hypoxia marker, expression in head and neck squamous cell carcinoma and its relationship to hypoxia, necrosis, and microvessel density. Cancer Res 61:5262–5267PubMedGoogle Scholar
  7. Beasley NJ, Leek R, Alam M et al (2002) Hypoxia-inducible factors HIF-1alpha and HIF-2alpha in head and neck cancer: relationship to tumor biology and treatment outcome in surgically resected patients. Cancer Res 62:2493–2497PubMedGoogle Scholar
  8. Bentzen SM, Gregoire V (2011) Molecular imaging-based dose painting: a novel paradigm for radiation therapy prescription. Sem Radiat Oncol 21:101–110CrossRefGoogle Scholar
  9. Birner P, Schindl M, Obermair A et al (2000) Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer Res 60:4693–4696PubMedGoogle Scholar
  10. Blasberg JD, Pass HI, Goparaju CM et al (2010) Reduction of elevated plasma osteopontin levels with resection of non-small-cell lung cancer. J Clin Oncol 28:936–941PubMedPubMedCentralCrossRefGoogle Scholar
  11. Braun RD, Lanzen JL, Snyder SA, Dewhirst MW (2001) Comparison of tumor and normal tissue oxygen tension measurements using Oxylite or microelectrodes in rodents. Am J Physiol Heart Circ Physiol 280:H2533–H2544PubMedGoogle Scholar
  12. Brizel DM, Scully SP, Harrelson JM et al (1996) Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res 56:941–943PubMedGoogle Scholar
  13. Brizel DM, Sibley GS, Prosnitz LR, Scher RL, Dewhirst MW (1997) Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 38:285–289PubMedCrossRefGoogle Scholar
  14. Burri P, Djonov V, Aebersold DM et al (2003) Significant correlation of hypoxia-inducible factor-1alpha with treatment outcome in cervical cancer treated with radical radiotherapy. Int J Radiat Oncol Biol Phys 56:494–501PubMedCrossRefGoogle Scholar
  15. Collingridge DR, Young WK, Vojnovic B et al (1997) Measurement of tumor oxygenation: a comparison between polarographic needle electrodes and a time-resolved luminescence-based optical sensor. Radiat Res 147:329–334PubMedCrossRefGoogle Scholar
  16. Cooper RA, Carrington BM, Loncaster JA et al (2000) Tumour oxygenation levels correlate with dynamic contrast-enhanced magnetic resonance imaging parameters in carcinoma of the cervix. Radiother Oncol 57:53–59PubMedCrossRefGoogle Scholar
  17. De Schutter H, Landuyt W, Verbeken E et al (2005) The prognostic value of the hypoxia markers CA IX and GLUT 1 and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy ± chemotherapy. BMC Cancer 5:42PubMedPubMedCentralCrossRefGoogle Scholar
  18. Dearling JL, Lewis JS, Mullen GE, Rae MT, Zweit J, Blower PJ (1998) Design of hypoxia-targeting radiopharmaceuticals: selective uptake of copper-64 complexes in hypoxic cells in vitro. Eur J Nucl Med 25:788–792PubMedCrossRefGoogle Scholar
  19. Dehdashti F, Mintun MA, Lewis JS et al (2003) In vivo assessment of tumor hypoxia in lung cancer with 60Cu-ATSM. Eur J Nucl Med Mol Imaging 30:844–850PubMedCrossRefGoogle Scholar
  20. Dehdashti F, Grigsby PW, Lewis JS, Laforest R, Siegel BA, Welch MJ et al (2008) Assessing tumor hypoxia in cervical cancer by PET with 60Cu-labeled diacetyl-bis(N4-methylthiosemicarbazone). J Nucl Med 49:201–205PubMedCrossRefGoogle Scholar
  21. Dence CS, Ponde DE, Welch MJ, Lewis JS (2008) Autoradiographic and small-animal PET comparisons between (18)F-FMISO, (18)F-FDG, (18)F-FLT and the hypoxic selective (64)Cu-ATSM in a rodent model of cancer. Nucl Med Biol 35:713–720PubMedPubMedCentralCrossRefGoogle Scholar
  22. Dietz DW, Dehdashti F, Grigsby PW et al (2008) Tumor hypoxia detected by positron emission tomography with 60Cu-ATSM as a predictor of response and survival in patients undergoing neoadjuvant chemoradiotherapy for rectal carcinoma: a pilot study. Dis Colon Rectum 51:1641–1648PubMedCrossRefGoogle Scholar
  23. Dirix P, Vandecaveye V, De Keyzer F, Stroobants S, Hermans R, Nuyts S (2009) Dose painting in radiotherapy for head and neck squamous cell carcinoma: value of repeated functional imaging with (18)F-FDG PET, (18)F-fluoromisonidazole PET, diffusion-weighted MRI, and dynamic contrast-enhanced MRI. J Nucl Med 50:1020–1027PubMedCrossRefGoogle Scholar
  24. Donaldson SB, Betts G, Bonington SC et al (2011) Perfusion estimated with rapid dynamic contrast-enhanced magnetic resonance imaging correlates inversely with vascular endothelial growth factor expression and pimonidazole staining in head-and-neck cancer: a pilot study. Int J Radiat Oncol Biol Phys 81:1176–1183PubMedCrossRefGoogle Scholar
  25. Eriksen JG, Overgaard J (2007) Lack of prognostic and predictive value of CA IX in radiotherapy of squamous cell carcinoma of the head and neck with known modifiable hypoxia: an evaluation of the DAHANCA 5 study. Radiother Oncol 83:383–388PubMedCrossRefGoogle Scholar
  26. Eschmann SM, Paulsen F, Bedeshem C et al (2007) Hypoxia-imaging with (18)F-Misonidazole and PET: changes of kinetics during radiotherapy of head-and-neck cancer. Radiother Oncol 83:406–410PubMedCrossRefGoogle Scholar
  27. Evans SM, Du KL, Chalian AA et al (2007) Patterns and levels of hypoxia in head and neck squamous cell carcinomas and their relationship to patient outcome. Int J Radiat Oncol Biol Phys 69:1024–1031PubMedPubMedCentralCrossRefGoogle Scholar
  28. Fedarko NS, Jain A, Karadag A et al (2001) Elevated serum bone sialoprotein and osteopontin in colon, breast, prostate, and lung cancer. Clin Cancer Res 7:4060–4066PubMedGoogle Scholar
  29. Fukumura D, Xu L, Chen Y, Gohongi T, Seed B, Jain RK (2001) Hypoxia and acidosis independently up-regulate vascular endothelial growth factor transcription in brain tumors in vivo. Cancer Res 61:6020–6024PubMedGoogle Scholar
  30. Fyles AW, Milosevic M, Wong R et al (1998) Oxygenation predicts radiation response and survival in patients with cervix cancer. Radiother Oncol 48:149–156PubMedCrossRefGoogle Scholar
  31. Fyles A, Milosevic M, Pintilie M et al (2006) Long-term performance of interstitial fluid pressure and hypoxia as prognostic factors in cervix cancer. Radiother Oncol 80:132–137PubMedCrossRefGoogle Scholar
  32. Gatenby RA, Kessler HB, Rosenblum JS et al (1988) Oxygen distribution in squamous cell carcinoma metastases and its relationship to outcome of radiation therapy. Int J Radiat Oncol Biol Phys 14:831–838PubMedCrossRefGoogle Scholar
  33. Giatromanolaki A, Koukourakis MI, Sivridis E et al (2001) Expression of hypoxia-inducible carbonic anhydrase-9 relates to angiogenic pathways and independently to poor outcome in non-small cell lung cancer. Cancer Res 61:7992–7998PubMedGoogle Scholar
  34. Graeber T, Osmanian C, Jacks T et al (1996) Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumors. Nature 379(6560):88–91PubMedCrossRefGoogle Scholar
  35. Griffiths JR, Robinson SP (1999) The oxylite: a fibre-optic oxygen sensor. Br J Radiol 72:627–630PubMedCrossRefGoogle Scholar
  36. Güttler A, Giebler M, Cuno P et al (2013) Osteopontin and splice variant expression level in human malignant glioma: radiobiologic effects and prognosis after radiotherapy. Radiother Oncol 108:535–540PubMedCrossRefGoogle Scholar
  37. Hall EJ (1988) Radiobiology for the radiologist. Lippincott, PhiladelphiaGoogle Scholar
  38. Haugland HK, Vukovic V, Pintilie M et al (2002) Expression of hypoxia-inducible factor-1alpha in cervical carcinomas: correlation with tumor oxygenation. Int J Radiat Oncol Biol Phys 53:854–861PubMedCrossRefGoogle Scholar
  39. Hoebers FJP, Janssen HLK, Valdés Olmos RA et al (2002) Phase 1 study to identify tumour hypoxia in patients with head and neck cancer using technetium-99 m BRU 59-21. Eur J Nucl Med 29:1206–1211CrossRefGoogle Scholar
  40. Hoeckel M, Knoop C, Schlenger K et al (1993) Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. Radiother Oncol 26:45–50CrossRefGoogle Scholar
  41. Hoeckel M, Schlenger K, Aral B, Mitze M, Schaffer U, Vaupel P (1996) Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 56:4509–4515Google Scholar
  42. Horsman MR, Overgaard J (2007) Hyperthermia: a potent enhancer of radiotherapy. Clin Oncol 19:418–426CrossRefGoogle Scholar
  43. Horsman MR, Overgaard J, Siemann DW (2011) Impact on radiotherapy. In: Siemann DW (ed) Tumor Microenvironment. Wiley, ChichesterGoogle Scholar
  44. Horsman MR, Mortensen LS, Petersen JB, Busk M, Overgaard J (2012) Imaging hypoxia to improve radiotherapy outcome. Nat Rev Clin Oncol 9:674–687PubMedCrossRefGoogle Scholar
  45. Hui EP, Chan AT, Pezzella F et al (2002) Coexpression of hypoxia-inducible factors 1alpha and 2alpha, carbonic anhydrase IX, and vascular endothelial growth factor in nasopharyngeal carcinoma and relationship to survival. Clin Cancer Res 8:2595–2604PubMedGoogle Scholar
  46. Isa S, Kawaguchi T, Teramukai S et al (2009) Serum osteopontin levels are highly prognostic for survival in advanced non-small cell lung cancer: results from JMTO LC 0004. J Thorac Oncol 4:1104–1110PubMedCrossRefGoogle Scholar
  47. Ivanov S, Liao SY, Ivanova A et al (2001) Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer. Am J Pathol 158:905–919PubMedPubMedCentralCrossRefGoogle Scholar
  48. Jansen JFA, Schöder H, Lee NY et al (2010) Noninvasive assessment of tumor microenvironment using dynamic contrast-enhanced magnetic resonance imaging and 18F-fluoromisonidazole positron emission tomography imaging in neck nodal metastases. Int J Radiat Oncol Biol Phys 77:1403–1410PubMedCrossRefGoogle Scholar
  49. Jewell UR, Kvietikova I, Scheid A et al (2001) Induction of HIF-1alpha in response to hypoxia is instantaneous. FASEB J 15:1312–1314PubMedGoogle Scholar
  50. Jiang BH, Semenza GL, Bauer C et al (1996) Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension. Am J Physiol 271:C1172–C1180PubMedGoogle Scholar
  51. Kaanders JH, Wijffels KI, Marres HA et al (2002) Pimonidazole binding and tumor vascularity predict for treatment outcome in head and neck cancer. Cancer Res 62:7066–7074PubMedGoogle Scholar
  52. Khamly K, Choong P, Ngan S et al (2008) Hypoxia in soft-tissue sarcomas on [18F]-fluoroazomycin arabinoside positron emission tomography (FAZA-PET) powerfully predicts response to radiotherapy and early relapse (abstract 35029). Presented at the 14th Connective Tissue Oncology Society Annual Meeting, November 13–15 (London)Google Scholar
  53. Kikuchi M, Yamane T, Shinoharas S et al (2011) 18F-fluoromisonidazole positron emission tomography before treatment is a predictor of radiotherapy outcome and survival prognosis in patients with head and neck squamous cell carcinoma. Ann Nucl Med 25:625–633PubMedCrossRefGoogle Scholar
  54. Knocke TH, Weitmann HD, Feldmann HJ, Selzer E, Pötter R (1999) Intratumoral pO2-measurements as predictive assay in the treatment of carcinoma of the uterine cervix. Radiother Oncol 53:99–104PubMedCrossRefGoogle Scholar
  55. Kolstad P (1968) Intercapillary distance, oxygen tension and local recurrence in cervix cancer. Scand J Clin Lab Invest Suppl 106:145–157PubMedCrossRefGoogle Scholar
  56. Komar G, Seppänen M, Eskola O et al (2008) 18F-EF5: a new PET tracer for imaging hypoxia in head and neck cancer. J Nucl Med 49:1944–1951PubMedCrossRefGoogle Scholar
  57. Koopmann J, Fedarko NS, Jain A et al (2004) Evaluation of osteopontin as biomarker for pancreatic adenocarcinoma. Cancer Epidemiol Biomarkers Prev 13:487–491PubMedGoogle Scholar
  58. Krishna MC, Matsumoto S, Yasui H et al (2012) Electron paramagnetic resonance imaging of tumor pO2. Radiat Res 177:376–386PubMedCrossRefGoogle Scholar
  59. Lal A, Peters H, St Croix B et al (2001) Transcriptional response to hypoxia in human tumors. J Natl Cancer Inst 93:1337–1343PubMedCrossRefGoogle Scholar
  60. Le QT, Sutphin PD, Raychaudhuri S et al (2003) Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas. Clin Cancer Res 9:59–67PubMedGoogle Scholar
  61. Le QT, Chen E, Salim A et al (2006) Evaluation of tumor oxygenation and gene expression in patients with early stage non-small cell lung cancers. Clin Cancer Res 12:1507–1514PubMedCrossRefGoogle Scholar
  62. Lee S, Shin HJ, Han IO et al (2007) Tumor carbonic anhydrase 9 expression is associated with the presence of lymph node metastases in uterine cervical cancer. Cancer Sci 98:329–333PubMedCrossRefGoogle Scholar
  63. Lee N, Nehmeh S, Schöder H et al (2009) Prospective trial incorporating pre-/mid-treatment [18F]-misonidazole positron emission tomography for head-and-neck cancer patients undergoing concurrent chemoradiotherapy. Int J Radiat Oncol Biol Phys 75:101–108PubMedPubMedCentralCrossRefGoogle Scholar
  64. Lehtio K, Eskola O, Vijanen T et al (2004) Imaging perfusion and hypoxia with PET to predict radiotherapy response in head-and-neck cancer. Int J Radiat Oncol Biol Phys 59:971–982PubMedCrossRefGoogle Scholar
  65. Lewis JS, Welch MJ (2001) PET imaging of hypoxia. Quant J Nucl Med 45:183–188Google Scholar
  66. Li L, Yu J, Xing L et al (2006) Serial hypoxia imaging with 99mTc-HL91 SPECT to predict radiotherapy response in non small cell lung cancer. Amer J Clin Oncol 29:628–633CrossRefGoogle Scholar
  67. Li L, Hu M, Zhu H, Zhao W, Yang G, Yu J (2010) Comparison of 18F-Fluoroerythronitroimidazole and 18F-fluorodeoxyglucose positron emission tomography and prognostic value in locally advanced non-small-cell lung cancer. Clin Lung Cancer 11:335–340PubMedCrossRefGoogle Scholar
  68. Ling CC, Humm J, Larson S et al (2000) Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality. Int J Radiat Oncol Biol Phys 47:551–560PubMedCrossRefGoogle Scholar
  69. Loncaster JA, Harris AL, Davidson SE et al (2001) Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix. Cancer Res 61:6394–6399PubMedGoogle Scholar
  70. Loncaster JA, Carrington BM, Sykes JR et al (2002) Prediction of radiotherapy outcome using dynamic contrast enhanced MRI of carcinoma of the cervix. Int J Radiat Oncol Biol Phys 54:759–767PubMedCrossRefGoogle Scholar
  71. Lukacova S, Khalil AA, Overgaard J et al (2006) Relationship between radiobiological hypoxia in a C3H mouse mammary carcinoma and osteopontin levels in mouse serum. Int J Radiat Biol 81:937–944CrossRefGoogle Scholar
  72. Lyng H, Sundfør K, Tropé C, Rofstad EK (2000) Disease control of uterine cervical cancer: relationships to tumor oxygen tension, vascular density, cell density, and frequency of mitosis and apoptosis measured before treatment and during radiotherapy. Clin Cancer Res 6:1104–1112PubMedGoogle Scholar
  73. Lyng H, Vorren AO, Sundfør K et al (2001) Assessment of tumor oxygenation in human cervical carcinoma by use of dynamic Gd-DTPA-enhanced MR imaging. J Magn Reson Imaging 14:750–756PubMedCrossRefGoogle Scholar
  74. Mack PC, Redman MW, Chansky K et al (2008) Lower osteopontin plasma levels are associated with superior outcomes in advanced non-small-cell lung cancer patients receiving platinum-based chemotherapy: SWOG Study S0003. J Clin Oncol 26:4771–4776PubMedPubMedCentralCrossRefGoogle Scholar
  75. Mayer A, Hockel M, Vaupel P (2006) Endogenous hypoxia markers in locally advanced cancers of the uterine cervix: reality or wishful thinking? Strahlenther Onkol 182:501–510PubMedCrossRefGoogle Scholar
  76. Mayr NA, Wang JZ, Zhang D et al (2010) Longitudinal changes in tumor perfusion pattern during the radiation therapy course and its clinical impact in cervical cancer. Int J Radiat Oncol Biol Phys 77:502–508PubMedCrossRefGoogle Scholar
  77. Minagawa Y, Shizukuishi K, Koike I et al (2011) Assessment of tumor hypoxia by 62Cu-ATSM PET/CT as a predictor of response in head and neck cancer: a pilot study. Ann Nucl Med 25:339–345PubMedCrossRefGoogle Scholar
  78. Mortensen LS, Johansen J, Kallehauge J et al (2012) FAZA PET/CT hypoxia imaging in patients with squamous cell carcinoma of the head and neck treated with radiotherapy: results from the DAHANCA 24 trial. Radiother Oncol 105:14–20PubMedCrossRefGoogle Scholar
  79. Newbold K, Castellano I, Charles-Edwards E et al (2009) An exploratory study into the role of dynamic contrast-enhanced magnetic resonance imaging or perfusion computed tomography for detection of intratumoral hypoxia in head-and-neck cancer. Int J Radiat Oncol Biol Phys 74:29–37PubMedCrossRefGoogle Scholar
  80. Nielsen T, Wittenborn T, Horsman MR (2012) Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in preclinical studies of antivascular treatments. Pharmaceutics 4:563–589PubMedPubMedCentralCrossRefGoogle Scholar
  81. Nordsmark M, Overgaard M, Overgaard J (1996) Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. Radiother Oncol 41:31–39PubMedCrossRefGoogle Scholar
  82. Nordsmark M, Alsner J, Keller J et al (2001) Hypoxia in human soft tissue sarcomas: adverse impact on survival and no association with p53 mutations. Br J Cancer 84:1070–1075PubMedPubMedCentralCrossRefGoogle Scholar
  83. Nordsmark M, Bentzen SM, Rudat V et al (2005) Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study. Radiother Oncol 77:18–24PubMedCrossRefGoogle Scholar
  84. Nordsmark M, Loncaster J, Aquino-Parsons C et al (2006) The prognostic value of pimonidazole and tumour pO2 in human cervix carcinomas after radiation therapy: a prospective international multi-center study. Radiother Oncol 80:123–131PubMedCrossRefGoogle Scholar
  85. Nordsmark M, Eriksen JG, Gebski V et al (2007) Differential risk assessments from five hypoxia specific assays: the basis for biologically adapted individualized radiotherapy in advanced head and neck cancer patients. Radiother Oncol 83:389–397PubMedCrossRefGoogle Scholar
  86. O’Donoghue JA, Zanzonico P, Pugachev A et al (2005) Assessment of regional tumor hypoxia using 18F-fluoromisonidazole and 64Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) positron emission tomography: Comparative study featuring microPET imaging, Po2 probe measurement, autoradiography, and fluorescent microscopy in the R3327-AT and FaDu rat tumor models. Int J Radiat Oncol Biol Phys 61:1493–1502PubMedCrossRefGoogle Scholar
  87. Ostheimer C, Bache M, Güttler A et al (2014) Osteopontin, carbonic anhydrase 9 and vascular endothelial growth factor. A pilot study on potential plasma hypoxia markers in the radiotherapy o non-small-cell lung cancer. Strahlenther Onkol 190:276–282Google Scholar
  88. Overgaard J (2007) Hypoxic radiosensitization: adored and ignored. J Clin Oncol 25:4066–4074PubMedCrossRefGoogle Scholar
  89. Overgaard J, Eriksen JG, Nordsmark M et al (2005) Plasma osteopontin, hypoxia, and response to the hypoxia sensitiser nimorazole in radiotherapy of head and neck cancer: results from the DAHANCA 5 randomised double-blind placebo-controlled trial. Lancet Oncol 6:757–764Google Scholar
  90. Pacheco-Torres J, López-Larrubia P, Ballesteros P, Cerdán S (2011) Imaging tumor hypoxia by magnetic resonance methods. NMR Biomed 24:1–16PubMedCrossRefGoogle Scholar
  91. Petrik D, Lavori PW, Cao H et al (2006) Plasma osteopontin is an independent prognostic marker for head and neck cancers. J Clin Oncol 24:5291–5297PubMedCrossRefGoogle Scholar
  92. Rajendran JG, Schwartz DL, O’Sullivan J et al (2006) Tumor hypoxia imaging with [F-18] fluoromisonidazole positron emission tomography in head and neck cancer. Clin Cancer Res 12:5435–5441PubMedPubMedCentralCrossRefGoogle Scholar
  93. Raleigh JA, Chou SC, Arteel GE, Horsman MR (1999) Comparisons among pimonidazole binding, oxygen electrode measurements and radiation response in C3H mouse tumors. Radiat Res 151:580–589PubMedCrossRefGoogle Scholar
  94. Rasey JS, Koh WJ, Evans ML et al (1996) Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. Int J Radiat Oncol Biol Phys 36:417–428PubMedCrossRefGoogle Scholar
  95. Reischl G, Dorow DS, Cullinane C et al (2007) Imaging of tumor hypoxia with [124I]IAZA in comparison with [18F]FMISO and [18F]FAZA–first small animal PET results. J Pharm Pharm Sci 10:203–211PubMedGoogle Scholar
  96. Rischin D, Hicks RJ, Fischer R et al (2006) Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine: a substudy of Trans-Tasman Radiation Oncology Group study 98.02. J Clin Oncol 24:2098–2104PubMedCrossRefGoogle Scholar
  97. Rudat V, Stadler P, Becker A et al (2001) Predictive value of the tumor oxygenation by means of pO2 histography in patients with advanced head and neck cancer. Strahlenther Onkol 177:462–468PubMedCrossRefGoogle Scholar
  98. Said HM, Katzer A, Flentje M, Vordermark D (2005) Response of the plasma hypoxia marker osteopontin to in vitro hypoxia in human tumor cells. Radiother Oncol 76:200–205PubMedCrossRefGoogle Scholar
  99. Schuetz M, Schmid MP, Pötter R et al (2010) Evaluating repetitive 18F-fluoroazomycin-arabinoside (18FAZA) PET in the setting of MRI guided adaptive radiotherapy in cervical cancer. Acta Oncol 49:941–947PubMedCrossRefGoogle Scholar
  100. Seddon BM, Honess DJ, Vojnovic B, Tozer GM, Workman P (2001) Measurement of tumor oxygenation: in vivo comparison of a luminescence fiber-optic sensor and a polarographic electrode in the p22 tumor. Radiat Res 155:837–846PubMedCrossRefGoogle Scholar
  101. Seddon BM, Payne GS, Simmons L et al (2003) A phase I study of SR-4554 via intravenous administration for noninvasive investigation of tumor hypoxia by magnetic resonance spectroscopy in patients with malignancy. Clin Cancer Res 9:5101–5112PubMedGoogle Scholar
  102. Snitcovsky I, Leitao GM, Pasini FS et al (2009) Plasma osteopontin levels in patients with head and neck cancer undergoing chemoradiotherapy. Arch Otolaryngol Head Neck Surg 135:807–811PubMedCrossRefGoogle Scholar
  103. Sorensen BS, Hao J, Overgaard J et al (2005) Influence of oxygen concentration and pH on expression of hypoxia induced genes. Radiother Oncol 76:187–193Google Scholar
  104. Søvik Å, Malinen E, Olsen DR (2009) Strategies for biologic image-guided dose escalation: a review. Int J Radiat Oncol Biol Phys 73:650–658PubMedCrossRefGoogle Scholar
  105. Spence AM, Muzi M, Swanson KR et al (2008) Regional hypoxia in glioblastoma multiforme quantified with [18F]fluoromisonidazole positron emission tomography before radiotherapy: correlation with time to progression and survival. Clin Cancer Res 14:2623–2630PubMedPubMedCentralCrossRefGoogle Scholar
  106. Stadler P, Becker A, Feldmann HJ et al (1999) Influence of the hypoxic subvolume on the survival of patients with head and neck cancer. Int J Radiat Oncol Biol Phys 44:749–754PubMedCrossRefGoogle Scholar
  107. Sundfør K, Lyng H, Rofstad EK (1998) Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix. Br J Cancer 78:822–827PubMedPubMedCentralCrossRefGoogle Scholar
  108. Swanson KR, Chakraborty G, Wang CH et al (2009) Complementary but distinct roles for MRI and 18F-fluoromisonidazole PET in the assessment of human glioblastomas. J Nucl Med 50:36–44PubMedCrossRefGoogle Scholar
  109. Swartz HM, Khan N, Buckey J et al (2004) Clinical applications of EPR: overview and perspectives. NMR Biomed 17:335–351PubMedCrossRefGoogle Scholar
  110. Talks KL, Turley H, Gatter KC et al (2000) The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol 157:411–421PubMedPubMedCentralCrossRefGoogle Scholar
  111. Thorwarth D, Eschmann SM, Scheiderbauer J, Paulsen F, Alber M (2005) Kinetic analysis of dynamic 18F-fluoromisonidazole PET correlates with radiation treatment outcome in head-and-neck cancer. BMC Cancer 5:152PubMedPubMedCentralCrossRefGoogle Scholar
  112. Thorwarth D, Eschmann SM, Holzner F, Paulsen F, Alber M (2006) Combined uptake of [18F]FDG and [18F]FMISO correlates with radiation therapy outcome in head-and-neck cancer patients. Radiother Oncol 80:151–156PubMedCrossRefGoogle Scholar
  113. Turaka A, Buyyounouski MK, Hanlon AL, Horwitz EM, Greenberg RE, Movsas B (2011) Hypoxic prostate/muscle Po2 ratio predicts for outcome in patients with localized prostate cancer: long-term results. Int J Radiat Oncol Biol Phys 82:e433–e439PubMedCrossRefGoogle Scholar
  114. Urano M, Chen Y, Humm J, Koutcher JA, Zanzonico P, Ling C (2002) Measurements of tumor tissue oxygen tension using a time-resolved luminescence-based optical oxylite probe: comparison with a paired survival assay. Radiat Res 158:167–173PubMedCrossRefGoogle Scholar
  115. Urtasun RC, Parliament MB, McEwan AJ et al (1996) Measurement of hypoxia in human tumours by non-invasive spect imaging of iodoazomycin arabinoside. Br J Cancer 74(Suppl.):S209–S212Google Scholar
  116. van Loon J, Janssen MHM, Öllers M et al (2010) PET imaging of hypoxia using [18F] HX4: a phase I trial. Eur J Nucl Med Mol Imaging 37:1663–1668PubMedCrossRefGoogle Scholar
  117. Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic micro-environment of human tumors: a review. Cancer Res 49:6449–6465PubMedGoogle Scholar
  118. Vävere AL, Lewis JS (2007) Cu-ATSM: a radiopharmaceutical for the PET imaging of hypoxia. Dalton Trans 21:4893–4902CrossRefGoogle Scholar
  119. Vikram DS, Zweier JL, Kuppusamy P (2007) Methods for noninvasive imaging of tissue hypoxia. Antioxid Redox Signal 9:1745–1756PubMedCrossRefGoogle Scholar
  120. Vordermark D, Brown JM (2003) Evaluation of hypoxia-inducible factor-1α (HIF-1α) as an intrinsic marker of tumor hypoxia in U87 MG human glioblastoma: in-vitro and xenograft studies. Int J Radiat Oncol Biol Phys 56:1184–1193PubMedCrossRefGoogle Scholar
  121. Vordermark D, Kaffer A, Riedl S et al (2005) Characterization of carbonic anhydrase IX (CA IX) as an endogenous marker of chronic hypoxia in live human tumor cells. Int J Radiat Oncol Biol Phys 61:1197–1207PubMedCrossRefGoogle Scholar
  122. Vukovic V, Haugland HK, Nicklee T et al (2001) Hypoxia-inducible factor-1alpha is an intrinsic marker for hypoxia in cervical cancer xenografts. Cancer Res 61:7394–7398PubMedGoogle Scholar
  123. Wen B, Urano M, Humm JL, Seshan VE, Li GC, Ling CC (2008) Comparison of helzel and oxylite systems in the measurement of tumor partial pressure (pO2). Radiat Res 169:67–75PubMedPubMedCentralCrossRefGoogle Scholar
  124. Wilson DF, Cerniglia GJ (1992) Localization of tumors and evaluation of their state of oxygenation by phosphorescence imaging. Cancer Res 52:3988–3993PubMedGoogle Scholar
  125. Winter SC, Shah KA, Han C et al (2006) The relation between hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha expression with anemia and outcome in surgically treated head and neck cancer. Cancer 107:757–766PubMedCrossRefGoogle Scholar
  126. Wykoff CC, Beasley NJ, Watson PH et al (2000) Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res 60:7075–7083Google Scholar
  127. Yuan H, Schroeder T, Bowsher JE, Hedlund LW, Wong T, Dewhirst MW (2006) Intertumoral differences in hypoxia selectivity of the PET imaging agent 64Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone). J Nucl Med 47:989–998PubMedGoogle Scholar
  128. Yue J, Yang Y, Cabrera AR et al (2012) Measuring tumor hypoxia with 18F-FETNIM PET in esophageal squamous cell carcinoma: a pilot clinical study. Dis Esophagus 25:54–61PubMedCrossRefGoogle Scholar
  129. Zhang H, Ye QH, Ren N et al (2006) The prognostic significance of preoperative plasma levels of osteopontin in patients with hepatocellular carcinoma. J Cancer Res Clin Oncol 132:709–717PubMedCrossRefGoogle Scholar
  130. Zhao D, Jiang L, Hahn EW, Mason RP (2005) Tumor physiologic response to combretastatin A4 phosphate assessed by MRI. Int J Radiat Oncol Biol Phys 62:872–880PubMedCrossRefGoogle Scholar
  131. Zhong H, De Marzo AM, Laughner E et al (1999) Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res 59:5830–5935PubMedGoogle Scholar
  132. Zhu Y, Denhardt DT, Cao H et al (2005) Hypoxia upregulates osteopontin expression in NIH-3T3 cells via a Ras-activated enhancer. Oncogene 24:6555–6563Google Scholar
  133. Zips D, Zöphel K, Abolmaali N et al (2012) Exploratory prospective trial of hypoxia imaging during radiochemotherapy in patients with locally advanced head-and-neck cancer. Radiother Oncol 105:21–28PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Universitätsklinik und Poliklinik für StrahlentherapieMartin-Luther-Universität Halle-WittenbergHalle/SaaleGermany
  2. 2.Department of Experimental Clinical OncologyAarhus University HospitalAarhusDenmark

Personalised recommendations