Positron Emission Tomography (PET) with fluorine-18 fluoromisonidazole (FMISO) has been used for several years as a non invasive imaging technique to study tumor hypoxia. Several experimental and clinical studies have indicated that FMISO uptake of tissues is correlated with tissue oxygen tension and that FMSO PET allows non-invasive differentiation between hypoxic and normoxic tumors. Currently, FMISO-PET represents the best characterized and validated noninvasive hypoxia imaging technique. Nevertheless, clinical studies have also shown the limitations of FMISO PET. Accumulation of FMISO in hypoxic tumors is relatively low, resulting in a low contrast between hypoxic tumors and surrounding normal tissues. In addition, imaging needs to be started relatively late after tracer injection (about 3 hours post-injection), when a significant percentage of the fluorine-18 label has already decayed and the count statistics of the PET images are relatively low. Because of these limitations, FMISO PET is still only used at a few research centers, despite high clinical interest in hypoxia imaging.