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Determination of tumour hypoxia with the PET tracer [18F]EF3: improvement of the tumour-to-background ratio in a mouse tumour model

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Abstract

Purpose

The 2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)acetamide (EF3) is a 2-nitroimidazole derivative which undergoes bioreductive activation under hypoxic conditions. Using the PET tracer [18F]EF3 in mice, tumour-to-muscle ratios ranging from 1.3 to 3.5 were observed. This study investigated the impact of various interventions aimed at increasing [18F]EF3 elimination, thus potentially increasing the tumour-to-noise ratio in mice, by increasing the renal filtration rate (spironolactone, furosemide), decreasing tubular re-absorption (metronidazole, ornidazole, amino acid solution) or stimulating gastro-intestinal elimination (phenobarbital).

Methods

C3H mice were injected i.v. with an average of 12.95 MBq of [18F]EF3. Drugs were injected i.v. 15 min before the tracer or daily 4 days prior to the experiment (phenobarbital). Anaesthetised mice were imaged from 30 to 300 min with a dedicated animal PET (Mosaic, Philips). Regions of interest were delineated around the tumour, bladder, heart, liver and leg muscle. Radioactivity was expressed as a percentage of injected activity per gram of tissue.

Results

Ornidazole decreased the urinary excretion and increased the liver uptake of [18F]EF3, but without causing any changes in the other organs. Phenobarbital significantly increased the liver concentration and decreased radioactivity in blood and muscle without affecting the tracer uptake in tumour. Consequently, a small but non-significant increase in tumour-to-noise ratio was observed. Although some effects were observed with other drugs, they did not modify the tumour-to-noise ratio.

Conclusion

Only phenobarbital induced a trend toward an increased tumour-to-noise ratio that could possibly be tested in the clinical situation.

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Acknowledgements

Nicolas Christian is a research fellow of the Fonds de la Recherche Scientifique of Belgium (F.R.I.A., Fonds pour la formation à la Recherche dans l’Industrie et l’Agriculture). The project was supported by a grant from the “Fonds Joseph Maisin”, Brussels, Belgium, by the European Commission’s Sixth Framework Programme funding (Contract no. LSHC-CT-2004-505785), and by a program project from the “Institut National du Cancer” of France (Project INCa N° RS 020).

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  1. Center for Molecular Imaging and Experimental Radiotherapy, Université Catholique de Louvain, Av Hippocrate, 10, Brussels, 1200, Brussels, Belgium

    Nicolas Christian, Anne Bol, Marc De Bast, Daniel Labar, John Lee, Pierre Mahy & Vincent Grégoire

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  1. Nicolas Christian
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  2. Anne Bol
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  3. Marc De Bast
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  6. Pierre Mahy
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  7. Vincent Grégoire
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Correspondence to Nicolas Christian.

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Christian, N., Bol, A., De Bast, M. et al. Determination of tumour hypoxia with the PET tracer [18F]EF3: improvement of the tumour-to-background ratio in a mouse tumour model. Eur J Nucl Med Mol Imaging 34, 1348–1354 (2007). https://doi.org/10.1007/s00259-007-0376-7

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  • DOI: https://doi.org/10.1007/s00259-007-0376-7

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