Quantifying tumour hypoxia with fluorine-18 fluoroerythronitroimidazole ([18F]FETNIM) and PET using the tumour to plasma ratio

Abstract. Fluorine-18 fluoroerythronitroimidazole ([18F]FETNIM) is a nitroimidazole compound that is potentially useful as a hypoxia marker in positron emission tomography (PET) studies of oncological patients. Our aim was to develop a simple protocol to quantitate uptake of [18F]FETNIM in hypoxic tumours. Dynamic imaging data from ten patients with head and neck cancer undergoing [18F]FETNIM PET was used in simulations and model fits to assess hypoxia marker uptake under different levels of blood flow. The distribution volume determined from dynamic PET study was compared with simple tumour to plasma and tumour to muscle ratios at 90–120 min. In skeletal muscle having a low but variable blood flow [2–6 ml/(100 g×min)], differences in hypoxia-specific uptake of [18F]FETNIM remain small and may be hard to detect with PET. At higher blood flow [>20 ml/(100 g×min)], the retention of [18F]FETNIM reflects the oxygenation status well and results in satisfactory contrast between hypoxic and well-oxygenated tissue. A good estimate of tissue hypoxia is accomplished by measuring the tissue to plasma [18F]FETNIM activity ratio using only a few late time points. The increased hypoxia-specific retention of [18F]FETNIM in tissues with high blood flow, such as malignant tumours, may facilitate application of [18F]FETNIM as a hypoxia marker in oncological patients. In the assessment of the tumour to non-target uptake ratio, plasma is the preferred reference tissue rather than muscle, which may show a more heterogeneous tracer uptake not easily controlled for.