Hypoxia positron emission tomography imaging with 18f-fluoromisonidazole.

The importance of hypoxia in disease pathogenesis and prognosis is gathering increasing clinical significance and having a greater impact on patient management and outcome. Previous efforts to evaluate hypoxia have included the invasive assessment of hypoxia with immunohistologic and histographic oxygen probes. The emergence of new radiotracers has allowed noninvasive assessment of hypoxia, with the most extensively investigated and validated positron emission tomography radiotracer of hypoxia to date being (18)F-fluoromisonodazole ((18)F-FMISO). This review discusses the relevance and biology of hypoxia in cells and organ systems, and reviews the laboratory and clinical applications of (18)F-FMISO in oncology and noncancer disease states.

[1]  A. Alavi,et al.  Noninvasive detection of tumor hypoxia using the 2-nitroimidazole [18F]EF1. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[2]  R. Jain.  Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy , 2005, Science.

[3]  R. Pötter,et al.  Intratumoral pO2-measurements as predictive assay in the treatment of carcinoma of the uterine cervix. , 1999, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[4]  K L Lindsley,et al.  Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography. , 1995, International journal of radiation oncology, biology, physics.

[5]  P Vaupel,et al.  Intratumoral pO2 histography as predictive assay in advanced cancer of the uterine cervix. , 1994, Advances in experimental medicine and biology.

[6]  P. Vaupel,et al.  Tumor tissue oxygenation as evaluated by computerized-pO2-histography. , 1990, International journal of radiation oncology, biology, physics.

[7]  A. Giaccia,et al.  The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. , 1998, Cancer research.

[8]  A. Fyles,et al.  Estimating hypoxic status in human tumors: a simulation using Eppendorf oxygen probe data in cervical cancer patients. , 2001, International journal of radiation oncology, biology, physics.

[9]  Morand Piert,et al.  Hypoxia-specific tumor imaging with 18F-fluoroazomycin arabinoside. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[10]  J. Karp,et al.  Noninvasive imaging of tumor hypoxia in rats using the 2-nitroimidazole 18F-EF5 , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[11]  C. Koch,et al.  [18F]-EF5, a marker for PET detection of hypoxia: synthesis of precursor and a new fluorination procedure. , 2001, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[12]  M. Eble,et al.  pO2 Polarography Versus Positron Emission Tomography ([18F] Fluoromisonidazole, [18F]-2-Fluoro-2’-Deoxyglucose) , 2004, Strahlentherapie und Onkologie.

[13]  B. Solomon,et al.  Modulation of intratumoral hypoxia by the epidermal growth factor receptor inhibitor gefitinib detected using small animal PET imaging , 2005, Molecular Cancer Therapeutics.

[14]  David L. Schwartz,et al.  Tumor Hypoxia Imaging with [F-18] Fluoromisonidazole Positron Emission Tomography in Head and Neck Cancer , 2006, Clinical Cancer Research.

[15]  H. Minn,et al.  Comparison of the biodistribution of two hypoxia markers [18F]FETNIM and [18F]FMISO in an experimental mammary carcinoma , 2004, European Journal of Nuclear Medicine and Molecular Imaging.

[16]  C Y Shiue,et al.  Synthesis of new hypoxia markers EF1 and [18F]-EF1. , 1999, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[17]  Stuart K. Calderwood,et al.  Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications , 2005, Cell stress & chaperones.

[18]  V. Oikonen,et al.  18F-Fluoroerythronitroimidazole radiation dosimetry in cancer studies. , 2002, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[19]  M Molls,et al.  Influence of the hypoxic subvolume on the survival of patients with head and neck cancer. , 1999, International journal of radiation oncology, biology, physics.

[20]  Y Yonekura,et al.  Copper-62-ATSM: a new hypoxia imaging agent with high membrane permeability and low redox potential. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[21]  Matthias Reimold,et al.  Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[22]  M J Welch,et al.  Evaluation of 64Cu-ATSM in vitro and in vivo in a hypoxic tumor model. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[23]  I. Flockhart,et al.  Pharmacokinetic and metabolic studies of the hypoxic cell radiosensitizer misonidazole. , 1978, Xenobiotica; the fate of foreign compounds in biological systems.

[24]  M. Dewhirst,et al.  Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. , 1999, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[25]  Heinz H. Coenen,et al.  pO(2) Polarography versus positron emission tomography ([(18)F] fluoromisonidazole, [(18)F]-2-fluoro-2'-deoxyglucose). An appraisal of radiotherapeutically relevant hypoxia. , 2004 .

[26]  K. Krohn,et al.  Synthesis and characterization of congeners of misonidazole for imaging hypoxia. , 1987, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[27]  G. Semenza,et al.  Molecular Events Implicated in Brain Tumor Angiogenesis and Invasion , 2000, Pediatric Neurosurgery.

[28]  Nathan Lawrentschuk,et al.  Assessing regional hypoxia in human renal tumours using 18F‐fluoromisonidazole positron emission tomography , 2005, BJU international.

[29]  Tove Grönroos,et al.  Quantifying tumour hypoxia with fluorine-18 fluoroerythronitroimidazole ([18F]FETNIM) and PET using the tumour to plasma ratio , 2002, European Journal of Nuclear Medicine and Molecular Imaging.

[30]  D. Abbott,et al.  Functional imaging of intratumoral hypoxia. , 2004, Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging.

[31]  Daniela Thorwarth,et al.  Combined uptake of [18F]FDG and [18F]FMISO correlates with radiation therapy outcome in head-and-neck cancer patients. , 2006, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[32]  Ren-Shyan Liu,et al.  Detection of anaerobic odontogenic infections by fluorine-18 fluoromisonidazole , 1996, European Journal of Nuclear Medicine.

[33]  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.

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

[35]  T L Phillips,et al.  Oxygen in human tumors: correlations between methods of measurement and response to therapy. Summary of a workshop held November 19-20, 1992, at the National Cancer Institute, Bethesda, Maryland. , 1993, Radiation research.

[36]  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.

[37]  T. Bezabeh,et al.  Advances in methods for assessing tumor hypoxia in vivo: Implications for treatment planning , 2006, Cancer and Metastasis Reviews.

[38]  E. Hall,et al.  Radiobiology for the radiologist , 1973 .

[39]  J. Rasey,et al.  Characteristics of the binding of labeled fluoromisonidazole in cells in vitro. , 1990, Radiation research.

[40]  O. S. Nielsen,et al.  The relationship between tumor oxygenation and cell proliferation in human soft tissue sarcomas. , 1996, International journal of radiation oncology, biology, physics.

[41]  D A Hilton,et al.  Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. , 1999, Cancer research.

[42]  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.

[43]  R. Fisher,et al.  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. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[44]  M. Graham,et al.  Fluorine-18-fluoromisonidazole radiation dosimetry in imaging studies. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[45]  P Vaupel,et al.  Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements. , 1991, Cancer research.

[46]  M. Alber,et al.  Imaging oxygenation of human tumours , 2006, European Radiology.

[47]  Jason S. Lewis,et al.  Dosimetry of 60/61/62/64Cu-ATSM: a hypoxia imaging agent for PET , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[48]  G. Donnan,et al.  Hypoxic tissue in ischaemic stroke: persistence and clinical consequences of spontaneous survival. , 2004, Brain : a journal of neurology.

[49]  David C. Reutens,et al.  Statistical Parametric Mapping of Hypoxic Tissue Identified by [18F]Fluoromisonidazole and Positron Emission Tomography Following Acute Ischemic Stroke , 2002, NeuroImage.

[50]  R. Hotchkiss,et al.  Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [18F]fluoromisonidazole. , 1991, The American journal of physiology.

[51]  H. Taniguchi,et al.  Relationships between oxygen and glucose metabolism in human liver tumours: positron emission tomography using 15O and 18F-deoxyglucose , 2004, Nuclear medicine communications.

[52]  P. Vaupel,et al.  Tumor hypoxia in pelvic recurrences of cervical cancer , 1998, International journal of cancer.

[53]  C. Dence,et al.  Myocardial kinetics of fluorine-18 misonidazole: a marker of hypoxic myocardium. , 1989, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[54]  V. Oikonen,et al.  Imaging of blood flow and hypoxia in head and neck cancer: initial evaluation with [(15)O]H(2)O and [(18)F]fluoroerythronitroimidazole PET. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[55]  P. Lambin,et al.  Oxygenation of head and neck tumors , 1993, Cancer.

[56]  M. Berridge,et al.  An efficient radiosynthesis of [18F]fluoromisonidazole. , 1993, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[57]  P. Vaupel,et al.  Hypoxia and Radiation Response in Human Tumors. , 1996, Seminars in radiation oncology.

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

[59]  F. Eschwège,et al.  Intratumoral oxygen tension in metastatic melanoma , 1997, Melanoma research.

[60]  I. Silver,et al.  Quantitative measurements of oxygen tension in normal tissues and in the tumours of patients before and after radiotherapy. , 1960, Acta radiologica.

[61]  G L Rosner,et al.  Pretreatment oxygenation profiles of human soft tissue sarcomas. , 1994, International journal of radiation oncology, biology, physics.

[62]  Rakesh K. Jain,et al.  Pathology: Cancer cells compress intratumour vessels , 2004, Nature.

[63]  T W Griffin,et al.  Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. , 1992, International journal of radiation oncology, biology, physics.

[64]  H. Minn,et al.  Pharmacokinetics of [18F]FETNIM: A Potential Hypoxia Marker for PET , 2001 .

[65]  J. Overgaard,et al.  Invasive oxygen measurements and pimonidazole labeling in human cervix carcinoma. , 2001, International journal of radiation oncology, biology, physics.

[66]  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.

[67]  H J Tochon-Danguy,et al.  The fate of hypoxic tissue on 18F‐fluoromisonidazole positron emission tomography after ischemic stroke , 2000, Annals of neurology.

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

[69]  D. Fraker,et al.  Tumor oxygenation status as a prognostic marker. , 2005, Cancer letters.

[70]  H. Lyng,et al.  Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix. , 1998, British Journal of Cancer.

[71]  J. Brown,et al.  Partition coefficient as a guide to the development of radiosensitizers which are less toxic than misonidazole. , 1980, Radiation research.

[72]  Marianne Patt,et al.  [18F]Fluoroazomycinarabinofuranoside (18FAZA) and [18F]Fluoromisonidazole (18FMISO): a comparative study of their selective uptake in hypoxic cells and PET imaging in experimental rat tumors. , 2003, Nuclear medicine and biology.

[73]  K. Krohn,et al.  Comparison of fluorine-18-fluorodeoxyglucose and tritiated fluoromisonidazole uptake during low-flow ischemia. , 1995, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[74]  H. Lyng,et al.  Oxygen tension in human tumours measured with polarographic needle electrodes and its relationship to vascular density, necrosis and hypoxia. , 1997, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[75]  J. Bowsher,et al.  Intertumoral differences in hypoxia selectivity of the PET imaging agent 64Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone). , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[76]  S. Berlangieri,et al.  Correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in gliomas using 18F-fluoromisonidazole, 18F-FDG PET, and immunohistochemical studies. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[77]  M. Eble,et al.  [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography in response evaluation after chemo-/radiotherapy of non-small-cell lung cancer: a feasibility study , 2006, BMC Cancer.

[78]  E. Rofstad,et al.  High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. , 2000, Cancer research.

[79]  C Clifton Ling,et al.  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 mo , 2005, International journal of radiation oncology, biology, physics.

[80]  Rakesh K. Jain,et al.  Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy , 2001, Nature Medicine.

[81]  M. Graham,et al.  Noninvasive detection of hypoxic myocardium using fluorine-18-fluoromisonidazole and positron emission tomography. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[82]  Y. Yonekura,et al.  Intra-tumoral distribution of (64)Cu-ATSM: a comparison study with FDG. , 2003, Nuclear medicine and biology.

[83]  Jean Charles Gilbert,et al.  Hypoxia in human gliomas: demonstration by PET with fluorine-18-fluoromisonidazole. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[84]  P. Vaupel,et al.  Hypoxic cervical cancers with low apoptotic index are highly aggressive. , 1999, Cancer research.

[85]  S. Ametamey,et al.  Assessment of hypoxia and perfusion in human brain tumors using PET with 18F-fluoromisonidazole and 15O-H2O. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[86]  S. Stylli,et al.  Imaging and quantitation of the hypoxic cell fraction of viable tumor in an animal model of intracerebral high grade glioma using [18F]fluoromisonidazole (FMISO). , 2002, Nuclear medicine and biology.

[87]  O. S. Nielsen,et al.  Tumour oxygenation assessed by 18F-fluoromisonidazole PET and polarographic needle electrodes in human soft tissue tumours. , 2003, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[88]  A. Harris,et al.  The molecular basis of the hypoxia response pathway: Tumour hypoxia as a therapy target , 1998, Cancer and Metastasis Reviews.

[89]  G M Tozer,et al.  Hypoxia modulated gene expression: angiogenesis, metastasis and therapeutic exploitation. , 2000, European journal of cancer.

[90]  H J Tochon-Danguy,et al.  No evidence of hypoxic tissue on 18F-fluoromisonidazole PET after intracerebral hemorrhage , 1999, Neurology.

[91]  R. Gatenby,et al.  Oxygen tension in human tumors: in vivo mapping using CT-guided probes. , 1985, Radiology.

[92]  C Weigel,et al.  Oxygenation of squamous cell carcinoma of the head and neck: comparison of primary tumors, neck node metastases, and normal tissue. , 1998, International journal of radiation oncology, biology, physics.

[93]  Geoffrey Donnan,et al.  Penumbral topography in human stroke: methodology and validation of the ‘Penumbragram’ , 2004, NeuroImage.

[94]  J. Eary,et al.  [18F]FMISO and [18F]FDG PET imaging in soft tissue sarcomas: correlation of hypoxia, metabolism and VEGF expression , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[95]  A. Scott,et al.  Lack of correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in non-small cell lung cancer assessed by 18F-Fluoromisonidazole and 18F-FDG PET. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[96]  James L Tatum,et al.  Hypoxia: Importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy , 2006, International journal of radiation biology.

[97]  R. Fisher,et al.  Phase I trial of concurrent tirapazamine, cisplatin, and radiotherapy in patients with advanced head and neck cancer. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[98]  G. Powis,et al.  Hypoxia inducible factor as a cancer drug target. , 2003, Current cancer drug targets.

[99]  P. Glazer,et al.  Genetic instability induced by the tumor microenvironment. , 1996, Cancer research.

[100]  P. Vaupel,et al.  Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. , 2001, Journal of the National Cancer Institute.

[101]  H. Lyng,et al.  Hypoxia-induced treatment failure in advanced squamous cell carcinoma of the uterine cervix is primarily due to hypoxia-induced radiation resistance rather than hypoxia-induced metastasis , 2000, British Journal of Cancer.

[102]  J. Bourhis,et al.  Predictive assays of radiation response in patients with head and neck squamous cell carcinoma: a review of the Institute Gustave Roussy experience. , 1997, International journal of radiation oncology, biology, physics.

[103]  Martin Westhofen,et al.  FDG—a marker of tumour hypoxia? A comparison with [18F]fluoromisonidazole and pO2-polarography in metastatic head and neck cancer , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[104]  P Lambin,et al.  Hypoxia as a target for combined modality treatments. , 2002, European journal of cancer.

[105]  A. Fyles,et al.  Oxygenation predicts radiation response and survival in patients with cervix cancer. , 1998, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[106]  D. Abbott,et al.  Identifying hypoxic tissue after acute ischemic stroke using PET and 18F-fluoromisonidazole , 1998, Neurology.

[107]  Lester J. Peters,et al.  Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent , 2005, European Journal of Nuclear Medicine and Molecular Imaging.