Imaging tumor hypoxia to advance radiation oncology.

SIGNIFICANCE: Most solid tumors contain regions of low oxygenation or hypoxia. Tumor hypoxia has been associated with a poor clinical outcome and plays a critical role in tumor radioresistance. RECENT ADVANCES: Two main types of hypoxia exist in the tumor microenvironment: chronic and cycling hypoxia. Chronic hypoxia results from the limited diffusion distance of oxygen, and cycling hypoxia primarily results from the variation in microvessel red blood cell flux and temporary disturbances in perfusion. Chronic hypoxia may cause either tumor progression or regressive effects depending on the tumor model. However, there is a general trend toward the development of a more aggressive phenotype after cycling hypoxia. With advanced hypoxia imaging techniques, spatiotemporal characteristics of tumor hypoxia and the changes to the tumor microenvironment can be analyzed. CRITICAL ISSUES: In this review, we focus on the biological and clinical consequences of chronic and cycling hypoxia on radiation treatment. We also discuss the advanced non-invasive imaging techniques that have been developed to detect and monitor tumor hypoxia in preclinical and clinical studies. FUTURE DIRECTIONS: A better understanding of the mechanisms of tumor hypoxia with non-invasive imaging will provide a basis for improved radiation therapeutic practices.