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Determination of tumour hypoxia with [18F]EF3 in patients with head and neck tumours: a phase I study to assess the tracer pharmacokinetics, biodistribution and metabolism

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Abstract

Purpose

The aim of this study was to assess the pharmacokinetics, biodistribution and metabolism of [18F]EF3, a labelled 2-nitroimidazole hypoxia marker, in ten patients with head and neck cancer.

Methods

[18F]EF3 was administered intravenously (group 1, n = 5, mean dose ± SD: 324 ± 108 MBq; group 2, n = 5, mean dose ± SD: 1,134 ± 138 MBq) to patients (nine male, one female). Blood and urine samples and whole-body PET scans were obtained from 20 s to 4–6 h. Radioactivity was determined in several regions of interest.

Results

No serious adverse event was reported. [18F]EF3 concentration in blood exhibited a bi-exponential decline. [18F]EF3 was mainly eliminated in the urine. By 7 h 40 min after injection, 53 ± 14% of the injected dose was collected in the urine. There was no significant difference between the low- and high-dose groups. A progressive accumulation occurred also in the colon, indicating a hepatobiliary excretion. Except in organs involved in the elimination of [18F]EF3, the tumour-to-organ ratio remained close to or below unity in muscle, lungs, heart and brain at various times after injection. In one patient, tumour hypoxia was observed with a tumour-to-blood ratio ranging from 1.4 to 1.9. Last, [18F]EF3 remained very stable after injection, with percentage of native tracer above 87% in the serum and 84% in the urine.

Conclusion

Administration of [18F]EF3 in head and neck cancer patients is feasible and safe. Uptake and retention in tumour was observed, indicating the presence of hypoxia.

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Acknowledgements

This work was supported by research grants from the “Fonds de la Recherche Scientifique Médicale” (grants # 3.4571.95, 3.4610.99 and 3.4560.00) of Belgium and by grants from the “Fonds Joseph Maisin”, Brussels and the “Fondation Albert Joachim”, Herent, Belgium.

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Authors and Affiliations

  1. Oral and Maxillofacial Surgery Department, Université catholique de Louvain, St-Luc University Hospital, 1200, Brussels, Belgium

    P. Mahy

  2. Centre for Molecular Imaging and Experimental Radiotherapy, Université catholique de Louvain, 1200, Brussels, Belgium

    P. Mahy, X. Geets, M. Lonneux, P. Levêque, N. Christian, M. De Bast, J. Gillart, D. Labar, J. Lee & V. Grégoire

  3. Radiation Oncology Department, Université catholique de Louvain, St-Luc University Hospital, 10 Ave Hippocrate, 1200, Brussels, Belgium

    X. Geets & V. Grégoire

  4. Nuclear Medicine Department, Université catholique de Louvain, St-Luc University Hospital, 1200, Brussels, Belgium

    M. Lonneux

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  1. P. Mahy
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Correspondence to V. Grégoire.

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P. Mahy and X. Geets contributed equally to this paper.

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Mahy, P., Geets, X., Lonneux, M. et al. Determination of tumour hypoxia with [18F]EF3 in patients with head and neck tumours: a phase I study to assess the tracer pharmacokinetics, biodistribution and metabolism. Eur J Nucl Med Mol Imaging 35, 1282–1289 (2008). https://doi.org/10.1007/s00259-008-0742-0

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