Skip to main content
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 10/2009

01.10.2009 | Original Article

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

verfasst von: Ernst J. Postema, Alexander J. B. McEwan, Terence A. Riauka, Piyush Kumar, Dacia A. Richmond, Douglas N. Abrams, Leonard I. Wiebe

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 10/2009

Einloggen, um Zugang zu erhalten

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.
Literatur
3.
Zurück zum Zitat 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 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
4.
Zurück zum Zitat 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 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
6.
Zurück zum Zitat 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 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
7.
Zurück zum Zitat 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 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
9.
Zurück zum Zitat Wiebe LI, Stypinski D. Pharmacokinetics of SPECT radiopharmaceuticals for imaging hypoxic tissues. Q J Nucl Med 1996;40:270–84.PubMed Wiebe LI, Stypinski D. Pharmacokinetics of SPECT radiopharmaceuticals for imaging hypoxic tissues. Q J Nucl Med 1996;40:270–84.PubMed
10.
Zurück zum Zitat 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.PubMedCrossRef 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/​0284186007500133​20.PubMedCrossRef
12.
Zurück zum Zitat 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 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
13.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
14.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
15.
Zurück zum Zitat 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 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
16.
Zurück zum Zitat 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 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
17.
Zurück zum Zitat 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. 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.
18.
Zurück zum Zitat 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 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
19.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
20.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
22.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
23.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
24.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
25.
Zurück zum Zitat 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 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
26.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
28.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
Metadaten
Titel
Initial results of hypoxia imaging using 1-α-d-(5-deoxy-5-[18F]-fluoroarabinofuranosyl)-2-nitroimidazole (18F-FAZA)
verfasst von
Ernst J. Postema
Alexander J. B. McEwan
Terence A. Riauka
Piyush Kumar
Dacia A. Richmond
Douglas N. Abrams
Leonard I. Wiebe
Publikationsdatum
01.10.2009
Verlag
Springer-Verlag
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 10/2009
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-009-1154-5

Weitere Artikel der Ausgabe 10/2009

European Journal of Nuclear Medicine and Molecular Imaging 10/2009 Zur Ausgabe