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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 4/2004

01-04-2004 | Original Article

Comparison of the biodistribution of two hypoxia markers [18F]FETNIM and [18F]FMISO in an experimental mammary carcinoma

Authors: Tove Grönroos, Lise Bentzen, Päivi Marjamäki, Rumi Murata, Michael R. Horsman, Susanne Keiding, Olli Eskola, Merja Haaparanta, Heikki Minn, Olof Solin

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 4/2004

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Abstract

The first aim of this study was to compare the hypoxia imaging ability of fluorine-18 fluoroerythronitroimidazole ([18F]FETNIM) with that of fluorine-18 fluoromisonimidazole ([18F]FMISO) in murine tumours of different sizes under two different oxygenation conditions. Secondly, we wanted to assess the biodistribution of the markers in normal tissues under similar conditions. Female CDF1 mice with a C3H mammary carcinoma grown on their backs were used. Tumours were size matched and animals breathed either normal air (21% O2) or carbogen gas (95% O2 + 5% CO2). The gassing procedure was begun 5 min before the intravenous injection of either [18F]FETNIM or [18F]FMISO and continued until the mice were sacrificed at 120 min. Blood, tumour, muscle, heart, lung, liver, kidney and fat were removed, counted for radioactivity and weighed. The tumour and muscle were frozen and cut with a cryomicrotome into sections. The spatial distribution of radioactivity from the tissue sections was determined with digital autoradiography. Estimation of the necrotic fraction was made on sections from formalin-fixed tumours. Digital autoradiography showed that the whole tumour-to-muscle radioactivity uptake ratios were significantly higher in normal air-breathing mice than in carbogen-treated mice for both [18F]FETNIM (4.9±2.6 vs 1.8±0.5; P<0.01) and [18F]FMISO (4.4±1.0 vs 1.5±0.4; P<0.01). The carbogen treatment had only slight effects on the biodistribution of either marker in normal tissues. The necrotic fraction determined in tumours did not correlate with the tumour volume or with the tumour-to-muscle radioactivity uptake ratio. This study shows that the uptake of both [18F]FETNIM and [18F]FMISO correlates with the oxygenation status in tumours. In addition, our data show no significant difference in the intratumoral uptake between the two markers. However, significantly higher radioactivity uptake values were measured for [18F]FMISO than for [18F]FETNIM in normal tissues.
Literature
1.
Moulder JE, Rockwell S. Hypoxic fractions of solid tumors: experimental techniques, methods of analysis, and a survey of existing data. Int J Radiat Oncol Biol Phys 1984; 10:695–712.PubMed
2.
Overgaard J, Horsman MR. Modification of hypoxia induced radioresistance in tumours by the use of oxygen and sensitizers. Semin Radiat Oncol 1996; 6:10–21.PubMed
3.
Chaplin DJ, Horsman MR, Trotter MJ, Siemann DW. Therapeutic significance of microenvironmental factors. In: Molls M, Vaupel P, eds. Medical radiobiology: blood perfusion and microenvironment of human tumours. Heidelberg Berlin New York: Springer; 1998:133–143.
4.
Höckel M, Schlenger K, Aral B, Mitze M, Schäffer U, Vaupel P. Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 1996; 56:4509–4515.PubMed
5.
Nordsmark M, Overgaard J. A confirmatory prognostic study on oxygenation status and loco-regional control in advanced head and neck squamous cell carcinoma treated by radiation therapy. Radiother Oncol 2000; 57:39–43.CrossRefPubMed
6.
7.
Chapman JD, Engelhardt EL, Stobbe CC, Schneider RF, Hanks GE. Measuring hypoxia and predicting tumor radioresistance with nuclear medicine assays. Radiother Oncol 1998; 46:229–237.CrossRefPubMed
8.
Varghese AJ, Gulyas S, Mohindra JK. Hypoxia-dependent reduction of 1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol by Chinese hamster ovary cells and KHT tumor cells in vitro and in vivo. Cancer Res 1976; 36:3761–3765.PubMed
9.
Chapman JD. Hypoxic sensitizers—implications for radiation therapy. N Engl J Med 1979; 301:1429–1432.PubMed
10.
Chapman JD, Franko AJ, Sharplin J. A marker for hypoxic cells in tumours with potential clinical applicability. Br J Cancer 1981; 43:546–550.PubMed
11.
Franko AJ, Chapman JD. Binding of14C-misonidazole to hypoxic cells in V79 spheroids. Br J Cancer 1982; 45:694–699.PubMed
12.
Raleigh JA, Franko AJ, Koch CJ, Born JL. Binding of misonidazole to hypoxic cells in monolayer and spheroid culture: evidence that a side-chain label is bound as efficiently as a ring label. Br J Cancer 1985; 51:229–235.PubMed
13.
Rasey J, Koh WJ, Grierson JR, Grunbaum Z, Krohn KA. Radiolabeled fluoromisonidazole as an imaging agent for tumor hypoxia. Int J Radiation Oncology Biol Phys 1989; 17:985–991.
14.
Kubota K, Tada M, Yamada S, Hori K, Saito S, Iwata R, Sato K, Fukuda H, Ido T. Comparison of the distribution of fluorine-18 fluoromisonidazole, deoxyglucose and methionine in tumour tissue. Eur J Nucl Med 1999; 26:750–757.CrossRefPubMed
15.
Rasey J, Casciari JJ, Hofstrand PD, Muzi M, Graham MM, Chin LK. Determining hypoxic fraction in a rat glioma by uptake of radiolabeled fluoromisonidazole. Radiat Res 2000; 153:84–92.PubMed
16.
Bentzen L, Keiding S, Horsman MR, Falborg L, Hansen SB, Overgaard J. Feasibility of detecting hypoxia in experimental mouse tumours with18F-fluorinated tracers and positron emission tomography; a study evaluating [18F]fluoromisonidazole and [18F]fluoro-2-deoxyglucose. Acta Oncol 2000; 39:629–637.CrossRefPubMed
17.
Tochon-Danguy HJ, Sachinidis JI, Chan F, Gordon Chan J, Hall C, Cher L, Stylli S, Hill J, Kaye A, Scott AM. Imaging and quantitation of the hypoxic cell fraction of viable tumor in an animal model of intracerebral high grade glioma using [18F]fluoromisonidazole (FMISO). Nucl Med Biol 2002; 29:191–197.CrossRefPubMed
18.
Bentzen L, Keiding S, Horsman MR, Gronroos T, Hansen SB, Overgaard J. Assessment of hypoxia in experimental mice tumours by [18F]fluoromisonidazole PET and pO2 electrode measurements: influence of tumour volume and carbogen breathing. Acta Oncol 2002; 41:304–312.CrossRefPubMed
19.
Koh WJ, Rasey JS, Evans ML, Grierson JR, Lewellen TK, Graham MM, Krohn KA, Griffin TW. Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. Int J Radiat Oncol Biol Phys 1992; 22:199–212.PubMed
20.
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; 33:2133–2137.PubMed
21.
Rasey JS, Koh WJ, Evans ML, Peterson LM, Lewellen TK, Graham MM, Krohn KA. 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 1996; 36:417–428.PubMed
22.
Yeh SH, Liu RS, Wu LC, Yang DJ, Yen SH, Chang CW, Yu TW, Chou KL, Chen KY. Fluorine-18 fluoromisonidazole tumour to muscle retention ratio for the detection of hypoxia in nasopharyngeal carcinoma. Eur J Nucl Med 1996; 23:1378–1383.PubMed
23.
Rajendran JG, Wilson DC, Conrad EU, Peterson LM, Bruckner JD, Rasey JS, Chin LK, Hofstrand PD, Grierson JR, Eary JF, Krohn KA. [18F]FMISO and [18F]FDG PET imaging in soft tissue sarcomas: correlation of hypoxia, metabolism and VEGF expression. Eur J Nucl Med Mol Imaging 2003; 30:695–704.PubMed
24.
Bentzen L, Keiding S, Nordsmark M, Falborg L, Hansen SB, Keller J, Nielsen OS, Overgaard J. Tumour oxygenation assessed by 18F-fluoromisonidazole PET and polarographic needle electrodes in human soft tissue tumours. Radiother Oncol 2003; 67:339–344.CrossRefPubMed
25.
Yang DJ, Wallace S, Cherif A, Chun L, Gretzer MB, Kim EE, Podoloff DA. Development of F-18-labeled fluoroerythronitroimidazole as a PET agent for imaging tumor hypoxia. Radiology 1995; 194:795–800.PubMed
26.
Chung JK, Chang YS, Lee YJ, Kim YJ, Jeong JM, Lee DS, Jang JJ, Lee MC. The effect of tumor size on F-18-labeled fluorodeoxyglucose and fluoroerythronitroimidazole uptake in a murine sarcoma model. Ann Nucl Med 1999; 13:303–308.PubMed
27.
Grönroos T, Eskola O, Lehtiö K, Minn H, Marjamäki P, Bergman J, Haaparanta M, Forsback S, Solin O. Pharmacokinetics of [18F]FETNIM: a potential hypoxia marker for PET. J Nucl Med 2001; 42:1397–1404.
28.
Lehtiö K, Oikonen V, Grönroos T, Eskola O, Kalliokoski K, Bergman J, Solin O, Grénman R, Nuutila P, Minn H. Imaging of blood flow and hypoxia in head and neck cancer: initial evaluation with [15O]H2O and [18F]fluoroerythronitroimidazole PET. J Nucl Med 2001; 42:1643–1652.
29.
Lehtiö K, Oikonen V, Nyman S, Grönroos T, Roivanen A, Eskola O, Minn H. Quantifying tumor hypoxia with fluorine-18 fluoroerythronitroimidazole ([18F]FETNIM) and PET using tumor-to-plasma ratio. Eur J Nucl Med Mol Imaging 2003; 30:101–108.CrossRefPubMed
30.
Overgaard J. Simultaneous and sequential hyperthermia and radiation treatment of an experimental tumor and its surrounding normal tissue in vivo. Int J Radiat Oncol Biol Phys 1980; 6:1507–1517.PubMed
31.
Horsman MR, Khalil AA, Siemann DW, Grau C, Hill SA, Lynch EM, Chaplin DJ, Overgaard J. Relationship between radiobiological hypoxia in tumors and electrode measurements of tumor oxygenation. Int J Radiat Oncol Biol Phys 1994; 29:439–442.PubMed
32.
Olive PL, Horsman MR, Grau C, Overgaard J. Detection of hypoxic cells in a C3H mouse mammary carcinoma using the comet assay. Br J Cancer 1997; 76:694–699.PubMed
33.
Lim JL, Berridge MS. An efficient radiosynthesis of [18F]fluoromisonimidazole. Appl Radiat Isot 1993; 44:1085–1091.CrossRefPubMed
34.
Grau C, Horsman MR, Overgaard J. Influence of carboxyhemoglobin level on tumor growth, blood flow, and radiation response in an experimental model. Int J Radiat Oncol Biol Phys 1992; 22:421–424.PubMed
35.
Horsman MR, Siemann DW, Nordsmark M, Khalil AA, Overgaard J, Chaplin DJ. The combination of nicotinamide and carbogen breathing to improve tumour oxygenation prior to radiation treatment. In: Hogan MC, Mathieu-Costello O, Poole DC, Wagner PD, eds. Oxygen transport to tissue XVI. New York: Plenum; 1994:635–642.
36.
Lewis JS, McCarthy DW, McCarthy TJ, Fujibayashi Y, Welch M. Evaluation of64Cu-ATSM in vitro and in vivo in a hypoxic tumor model. J Nucl Med 1999; 40:177–183.
37.
Horsman MR, Khalil AA, Nordsmark M, Grau C, Overgaard J. Relationship between radiobiological hypoxia and direct estimates of tumour oxygenation in a mouse tumour model. Radiother Oncol 1993; 28:69–71.PubMed
38.
Nordsmark M, Grau C, Horsman MR, Jorgensen HS, Overgaard J. Relationship between tumour oxygenation, bioenergetic status and radiobiological hypoxia in an experimental model. Acta Oncol 1995; 34:329–334.PubMed
39.
Vaupel P, Kallinowski F, Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 1989; 49:6449–6465.PubMed
40.
Khalil AA, Horsman MR, Overgaard J. The importance of determining necrotic fraction when studying the effect of tumour volume on tissue oxygenation. Acta Oncol 1995; 34:297–300.PubMed
Metadata
Title
Comparison of the biodistribution of two hypoxia markers [18F]FETNIM and [18F]FMISO in an experimental mammary carcinoma
Authors
Tove Grönroos
Lise Bentzen
Päivi Marjamäki
Rumi Murata
Michael R. Horsman
Susanne Keiding
Olli Eskola
Merja Haaparanta
Heikki Minn
Olof Solin
Publication date
01-04-2004
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 4/2004
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-003-1404-x

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