Current preclinical and clinical applications of hypoxia PET imaging using 2-nitroimidazoles

Hypoxia is a common characteristic of solid tumors and is associated with poor prognosis. Positron emission tomography (PET) can visualize tumor hypoxia in a non-invasive, 3-dimensional manner and can be used to acquire information longitudinally. Multiple 2-nitroimidazole based PET tracers are developed, validated and quantified in the search for the ideal hypoxia tracer and several tracers have shown to reliably represent tumor hypoxia. Furthermore, multiple studies describe the prognostic value of hypoxia PET imaging and the ability to monitor hypoxia during treatment. These applications can be of great potential and their role in treatment planning and modification needs to be further assessed with respect to personalized chemoradiation therapy. In this review we focus on the tracers that were positively validated in preclinical and clinical studies and report accurate quantification and visualization of hypoxia. The characteristics of these tracers are summarized for both preclinical and clinical studies. Furthermore, the clinical applications of hypoxia PET imaging are addressed with a focus on the ability to reliably monitor tumor hypoxia during treatment and the prognostic potential. Also the feasibility studies for hypoxia guided intensity modulated radiation therapy and the patient stratification for hypoxia targeted drugs are assessed.