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.
OBJECTIVE
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.


CONCLUSIONS
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.
Mahy
P
P
Oral and Maxillofacial Surgery Department, Université catholique de Louvain, St-Luc University Hospital, 1200 Brussels, Belgium.
Geets
X
X
Lonneux
M
M
Levêque
P
P
Christian
N
N
De Bast
M
M
Gillart
J
J
Labar
D
D
Lee
J
J
Grégoire
V
V
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging; D005260:Female; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging*; D006801:Humans; D000860:Hypoxia / Q000000981:diagnostic imaging*; D007822:Laryngeal Neoplasms / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D009593:Nitroimidazoles / Q000493:pharmacokinetics*; D010610:Pharyngeal Neoplasms / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
C438056:2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)-acetamide; D009593:Nitroimidazoles; D019275:Radiopharmaceuticals