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

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.