Review of Positron Emission Tomography Tracers for Imaging of Tumor Hypoxia

Hypoxia plays a critical role in tumor development and aggressiveness and is an important prognostic factor for resistance to antineoplastic treatments; therefore, it is required to measure the hypoxic level of tumor for a favorable outcome. The pretherapy information on the oxygenation status of a tumor microenvironment should also have implications for treatment selection. A diffuse distribution of hypoxia in a tumor might suggest a benefit from a systemic approach, such as a hypoxic cell cytotoxin, tirapazamine, or antigrowth factor drugs to combat the limitations of hypoxia. Alternatively, a more focal hypoxia might benefit from a local/regional approach, such as intensity-modulated radiation therapy-based radiation dose escalation to the hypoxic subvolume. This review anticipates that ¹⁸F-FMISO (¹⁸F-fluoromisonodazole) and ⁶⁴Cu-ATSM-positron emission tomography (PET) will prove useful for selecting individual patients for the most appropriate treatment. The advent of new radiotracers has allowed noninvasive assessment of hypoxia, with the most extensively investigated and validated PET radiotracer for hypoxia to date being ¹⁸F-FMISO. This article discusses the relevance and biology of hypoxia in cells and organ systems and reviews the laboratory and clinical applications of ¹⁸F-FMISO and other agents in oncology.