Longitudinal PET imaging of tumor hypoxia during the course of radiotherapy.

Hypoxia results from an imbalance between oxygen supply and consumption. It is a common phenomenon in solid malignant tumors such as head and neck cancer. As hypoxic cells are more resistant to therapy, tumor hypoxia is an indicator for poor prognosis. Several techniques have been developed to measure tissue oxygenation. These are the Eppendorf O2 polarographic needle electrode, immunohistochemical analysis of endogenous (e.g., hypoxia-inducible factor-1α (HIF-1a)) and exogenous markers (e.g., pimonidazole) as well as imaging methods such as functional magnetic resonance imaging (e.g., blood oxygen level dependent (BOLD) imaging, T1-weighted imaging) and hypoxia positron emission tomography (PET). Among the imaging modalities, only PET is sufficiently validated to detect hypoxia for clinical use. Hypoxia PET tracers include 18F-fluoromisonidazole (FMISO), the most commonly used hypoxic marker, 18F-flouroazomycin arabinoside (FAZA), 18Ffluoroerythronitroimidazole (FETNIM), 18F-2-nitroimidazolpentafluoropropylacetamide (EF5) and 18F-flortanidazole (HX4). As technical development provides the opportunity to increase the radiation dose to subregions of the tumor, such as hypoxic areas, it has to be ensured that these regions are stable not only from imaging to treatment but also through the course of radiotherapy. The aim of this review is therefore to characterize the behavior of tumor hypoxia during radiotherapy for the whole tumor and for subregions by using hypoxia PET tracers, with focus on head and neck cancer patients.