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

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Mahy, Pierre [UCL] Geets, Xavier [UCL] Lonneux, Max [UCL] Levêque, Philippe [UCL] Christian, Nicolas [UCL] De Bast, Marc [UCL] Gillart, Jacques [UCL] Labar, Daniel [UCL] Lee, John Aldo [UCL] Grégoire, Vincent [UCL]

PURPOSE: The aim of this study was to assess the pharmacokinetics, biodistribution and metabolism of [(18)F]EF3, a labelled 2-nitroimidazole hypoxia marker, in ten patients with head and neck cancer. METHODS: [(18)F]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. [(18)F]EF3 concentration in blood exhibited a bi-exponential decline. [(18)F]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 [(18)F]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, [(18)F]EF3 remained very stable after injection, with percentage of native tracer above 87% in the serum and 84% in the urine. CONCLUSION: Administration of [(18)F]EF3 in head and neck cancer patients is feasible and safe. Uptake and retention in tumour was observed, indicating the presence of hypoxia.

Document type Article de périodique (Journal article) – Article de recherche – Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 2008
Language Anglais
Journal information "European Journal of Nuclear Medicine and Molecular Imaging" - Vol. 35, no. 7, p. 1282-1289 (2008)
Peer reviewed yes
Publisher Springer ((Germany) Heidelberg)
issn 1619-7070
e-issn 1619-7089
Publication status Publié
Affiliations UCL - Cliniques universitaires Saint-Luc
UCL - MD/MINT - Département de médecine interne
UCL - MD/FARM - Ecole de pharmacie
MESH Subject Tissue Distribution ; Radiopharmaceuticals - diagnostic use - pharmacokinetics ; Positron-Emission Tomography ; Pharyngeal Neoplasms - radionuclide imaging ; Nitroimidazoles - diagnostic use - pharmacokinetics ; Middle Aged ; Male ; Laryngeal Neoplasms - radionuclide imaging ; Humans ; Head and Neck Neoplasms - radionuclide imaging ; Female ; Carcinoma, Squamous Cell - radionuclide imaging ; Anoxia - radionuclide imaging ; Aged ; Adult
Links
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Bibliographic reference Mahy, Pierre ; Geets, Xavier ; Lonneux, Max ; Levêque, Philippe ; Christian, Nicolas ; et. al. Determination of tumour hypoxia with [(18)F]EF3 in patients with head and neck tumours : a phase I study to assess the tracer pharmacokinetics, biodistribution and metabolism. In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 35, no. 7, p. 1282-1289 (2008)
Permanent URL http://hdl.handle.net/2078.1/11311