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Initial results of hypoxia imaging using 1-α-d-(5-deoxy-5-[18F]-fluoroarabinofuranosyl)-2-nitroimidazole (18F-FAZA)

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Tumour hypoxia is thought to play a significant role in the outcome of solid tumour therapy. Positron emission tomography (PET) is the best-validated noninvasive technique able to demonstrate the presence of hypoxia in vivo. The locally developed PET tracer for imaging hypoxia, 1-α-d-(5-deoxy-5-[18F]-fluoroarabinofuranosyl)-2-nitroimidazole (18F-FAZA), has been shown to accumulate in experimental models of tumour hypoxia and to clear rapidly from the circulation and nonhypoxic tissues. The safety and general biodistribution patterns of this radiopharmaceutical in patients with squamous cell carcinoma of the head and neck (HNSCC), small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC), malignant lymphoma, and high-grade gliomas, were demonstrated in this study.

Methods

Patients with known primary or suspected metastatic HNSCC, SCLC or NSCLC, malignant lymphoma or high-grade gliomas were dosed with 5.2 MBq/kg of 18F-FAZA, then scanned 2–3 h after injection using a PET or PET/CT scanner. Images were interpreted by three experienced nuclear medicine physicians. The location and relative uptake scores (graded 0 to 4) of normal and abnormal 18F-FAZA biodistribution patterns, the calculated tumour-to-background (T/B) ratio, and the maximum standardized uptake value were recorded.

Results

Included in the study were 50 patients (32 men, 18 women). All seven patients with high-grade gliomas showed very high uptake of 18F-FAZA in the primary tumour. In six out of nine patients with HNSCC, clear uptake of 18F-FAZA was observed in the primary tumour and/or the lymph nodes in the neck. Of the 21 lymphoma patients (15 with non-Hodgkin’s lymphoma and 6 with Hodgkin’s disease), 3 demonstrated moderate lymphoma-related uptake. Of the 13 lung cancer patients (12 NSCLC, 1 SCLC), 7 had increased 18F-FAZA uptake in the primary lung tumour. No side effects of the administration of 18F-FAZA were observed.

Conclusion

This study suggests that 18F-FAZA may be a very useful radiopharmaceutical to image hypoxia in the tumour types selected. Especially the high uptake by gliomas was encouraging. Given the good imaging properties, including acceptable T/B ratios in the tumour categories studied, 18F-FAZA could be considered as a very promising agent for assessing the hypoxic fraction of these tumour types.

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References

  1. Höckel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 2001;93:266–76. doi:10.1093/jnci/93.4.266.

    Article  PubMed  Google Scholar 

  2. Höckel M, Knoop C, Schlenger K, Vorndran B, Baussmann E, Mitze M, et al. Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. Radiother Oncol 1993;26:45–50. doi:10.1016/0167-8140(93)90025-4.

    Article  PubMed  Google Scholar 

  3. Brizel DM, Sibley GS, Prosnitz LR, Scher RL, Dewhirst MW. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 1997;38:285–9. doi:10.1016/S0360-3016(97)00101-6.

    PubMed  CAS  Google Scholar 

  4. Nordsmark M, Hoyer M, Keller J, Nielsen OS, Jensen OM, Overgaard J. The relationship between tumor oxygenation and cell proliferation in human soft tissue sarcomas. Int J Radiat Oncol Biol Phys 1996;35:701–8. doi:10.1016/0360-3016(96)00132-0.

    PubMed  CAS  Google Scholar 

  5. Lee ST, Scott AM. Hypoxia positron emission tomography imaging with 18F-fluoromisonidazole. Semin Nucl Med 2007;37:451–61. doi:10.1053/j.semnuclmed.2007.07.001.

    Article  PubMed  Google Scholar 

  6. Urtasun RC, Parliament MB, McEwan AJ, Mercer JR, Mannan RH, Wiebe LI, et al. Measurement of hypoxia in human tumours by non-invasive spect imaging of iodoazomycin arabinoside. Br J Cancer Suppl 1996;27:S209–12.

    PubMed  CAS  Google Scholar 

  7. Grosu AL, Souvatzoglou M, Röper B, Dobritz M, Wiedenmann N, Jacob V, et al. Hypoxia imaging with FAZA-PET and theoretical considerations with regard to dose painting for individualization of radiotherapy in patients with head and neck cancer. Int J Radiat Oncol Biol Phys 2007;69:541–51. doi:10.1016/j.ijrobp.2007.05.079.

    PubMed  CAS  Google Scholar 

  8. Chapman JD. Measurement of tumor hypoxia by invasive and non-invasive procedures: a review of recent clinical studies. Radiother Oncol 1991;20(Suppl 1):13–9. doi:10.1016/0167-8140(91)90181-F.

    Article  PubMed  Google Scholar 

  9. Wiebe LI, Stypinski D. Pharmacokinetics of SPECT radiopharmaceuticals for imaging hypoxic tissues. Q J Nucl Med 1996;40:270–84.

    PubMed  CAS  Google Scholar 

  10. Bentzen L, Keiding S, Horsman MR, Falborg L, Hansen SB, Overgaard J. Feasibility of detecting hypoxia in experimental mouse tumours with 18F-fluorinated tracers and positron emission tomography – a study evaluating [18F]fluoro-2-deoxy-D-glucose. Acta Oncol 2000;39:629–37. doi:10.1080/028418600750013320.

    Article  PubMed  CAS  Google Scholar 

  11. Kumar P, Stypinski D, Xia H, McEwan AJB, Machulla HJ, Wiebe LI. Fluoroazomycin arabinoside (FAZA): synthesis, 2H and 3H-labelling and preliminary biological evaluation of a novel 2-nitroimidazole marker of tissue hypoxia. J Label Comp Radiopharmaceuticals 1999;42:3–16. doi:10.1002/(SICI)1099-1344(199901)42:1<3::AID-JLCR160>3.0.CO;2-H.

    Article  CAS  Google Scholar 

  12. Piert M, Machulla HJ, Picchio M, Reischl G, Ziegler S, Kumar P, et al. Hypoxia-specific tumor imaging with 18F-fluoroazomycin arabinoside. J Nucl Med 2005;46:106–13.

    PubMed  Google Scholar 

  13. Sorger D, Patt M, Kumar P, Wiebe LI, Barthel H, Seese A, 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. Nucl Med Biol 2003;30:317–26. doi:10.1016/S0969-8051(02)00442-0.

    Article  PubMed  CAS  Google Scholar 

  14. Spence AM, Muzi M, Swanson KR, O'Sullivan F, Rockhill JK, Rajendran JG, et al. Regional hypoxia in glioblastoma multiforme quantified with [18F]fluoromisonidazole positron emission tomography before radiotherapy: correlation with time to progression and survival. Clin Cancer Res 2008;14:2623–30. doi:10.1158/1078-0432.CCR-07-4995.

    Article  PubMed  CAS  Google Scholar 

  15. Bruehlmeier M, Roelcke U, Schubiger PA, Ametamey SM. Assessment of hypoxia and perfusion in human brain tumors using PET with 18F-fluoromisonidazole and 15O-H2O. J Nucl Med 2004;45:1851–9.

    PubMed  Google Scholar 

  16. Cher LM, Murone C, Lawrentschuk N, Ramdave S, Papenfuss A, Hannah A, et al. Correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in gliomas using 18F-fluoromisonidazole, 18F-FDG PET, and immunohistochemical studies. J Nucl Med 2006;47:410–8.

    PubMed  CAS  Google Scholar 

  17. Liu RS, Chu LS, Chu YK, Yen SH, Liao SQ, Yeh SH. Does h-oxidation occur in malignant neoplasm? A concurrent [C-11]acetate and [F-18]MISO study (abstract). J Nucl Med 1999;40:239P.

    Google Scholar 

  18. Valk PE, Mathis CA, Prados MD, Gilbert JC, Budinger TF. Hypoxia in human gliomas: demonstration by PET with fluorine-18-fluoromisonidazole. J Nucl Med 1992;33:2133–7.

    PubMed  CAS  Google Scholar 

  19. Brown JM, Workman P. Partition coefficient as a guide to the development of radiosensitizers which are less toxic than misonidazole. Radiat Res 1980;82:171–90. doi:10.2307/3575246.

    Article  PubMed  CAS  Google Scholar 

  20. Evans SM, Jenkins KW, Jenkins WT, Dilling T, Judy KD, Schrlau A, et al. Imaging and analytical methods as applied to the evaluation of vasculature and hypoxia in human brain tumors. Radiat Res 2008;170:677–90. doi:10.1667/RR1207.1.

    Article  PubMed  CAS  Google Scholar 

  21. Evans SM, Judy KD, Dunphy I, Jenkins WT, Hwang WT, Nelson PT, et al. Hypoxia is important in the biology and aggression of human glial brain tumors. Clin Cancer Res 2004;10:8177–84. doi:10.1158/1078-0432.CCR-04-1081.

    Article  PubMed  CAS  Google Scholar 

  22. Souvatzoglou M, Grosu AL, Roper B, Krause BJ, Beck R, Reischl G, et al. Tumour hypoxia imaging with [18F]FAZA PET in head and neck cancer patients: a pilot study. Eur J Nucl Med Mol Imaging 2007;34:1566–75. doi:10.1007/s00259-007-0424-3.

    Article  PubMed  CAS  Google Scholar 

  23. Hicks RJ, Rischin D, Fisher R, Binns D, Scott AM, Peters LJ. Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent. Eur J Nucl Med Mol Imaging 2005;32:1384–91. doi:10.1007/s00259-005-1880-2.

    Article  PubMed  Google Scholar 

  24. Rischin D, Hicks RJ, Fisher R, Binns D, Corry J, Porceddu S, 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. J Clin Oncol 2006;24:2098–104. doi:10.1200/JCO.2005.05.2878.

    Article  PubMed  Google Scholar 

  25. Cherk MH, Foo SS, Poon AM, Knight SR, Murone C, Papenfuss AT, 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. J Nucl Med 2006;47:1921–6.

    PubMed  CAS  Google Scholar 

  26. Wong TZ, Lacy JL, Petry NA, Hawk TC, Sporn TA, Dewhirst MW, et al. PET of hypoxia and perfusion with 62Cu-ATSM and 62Cu-PTSM using a 62Zn/62Cu generator. AJR Am J Roentgenol 2008;190:427–32. doi:10.2214/AJR.07.2876.

    Article  PubMed  Google Scholar 

  27. Yasuda H, Kaneta T, Takai Y, Nakayama K, Iwata R, Ito M, et al. Tumor hypoxia imaging with [F-18] fluoronitroimidazole in non-small-cell lung cancer. J Am Geriatr Soc 2007;55:1142–4. doi:10.1111/j.1532-5415.2007.01218.x.

    Article  PubMed  Google Scholar 

  28. Dehdashti F, Grigsby PW, Lewis JS, Laforest R, Siegel BA, Welch MJ. Assessing tumor hypoxia in cervical cancer by PET with 60Cu-labeled diacetyl-bis(N4-methylthiosemicarbazone). J Nucl Med 2008;49:201–205.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank the Regulatory Team – Margaret Landon, Sandra Gordey, Lai Schrader, Robert McQuarrie, and Merlita Lamadrid – of the Department of Oncologic Imaging at the Cross Cancer Institute for all their efforts collecting and processing the data. We would also like to thank the attending physicians of the Cross Cancer Institute, and Drs. Andrew Belch and Matthew Parliament in particular, for their ongoing support of this trial.

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Authors and Affiliations

  1. Department of Oncology, University of Alberta, 11560 University Avenue, Edmonton, Alberta, T6G 1Z2, Canada

    Ernst J. Postema, Alexander J. B. McEwan, Terence A. Riauka, Piyush Kumar, Dacia A. Richmond & Douglas N. Abrams

  2. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 1Z2, Canada

    Leonard I. Wiebe

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  1. Ernst J. Postema
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  2. Alexander J. B. McEwan
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Correspondence to Ernst J. Postema.

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Postema, E.J., McEwan, A.J.B., Riauka, T.A. et al. Initial results of hypoxia imaging using 1-α-d-(5-deoxy-5-[18F]-fluoroarabinofuranosyl)-2-nitroimidazole (18F-FAZA). Eur J Nucl Med Mol Imaging 36, 1565–1573 (2009). https://doi.org/10.1007/s00259-009-1154-5

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  • DOI: https://doi.org/10.1007/s00259-009-1154-5

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