Hypoxia Imaging for Radiation Therapy Planning

Hypoxia is one of the key features conferring resistance to oncologic treatment. Modern radiotherapy aims at overcoming hypoxia-induced resistance by escalating or redistributing dose or by modulating the sensitivity of poorly oxygenated but viable tumour cells. To accomplish this, it is necessary to detect hypoxia both spatially and temporally and to recognise limitations in sensitivity to differentiate oxic and hypoxic tumour subvolumes. Currently, PET/CT-based imaging using radiolabelled nitroimidazole or thiosemicarbazone compounds is the preferred technique for biological dose planning targeting hypoxia. Hypoxic tumour cells identified on PET/CT may be treated by giving a graded higher dose in a limited number of hypoxic compartments or by individually prescribing a dose to each volume unit based on 3D mapping of tumour oxygenation status. The latter technique is commonly called dose painting by numbers (DPN) to illustrate the heterogeneous dose received by the hypoxic target. Dose planning requires sophisticated computer algorithms where intensity-modulated radiotherapy (IMRT) is used to deliver irradiation. It is not yet known which strategy for planning and delivering hypoxia-targeted radiotherapy is the most appropriate in the clinical setting and what role chemical and biological modifiers of oxygenation will play given the lack of outcome data. Furthermore, adaptive strategies accounting for the effect of reoxygenation and cyclic hypoxia should be studied as well. This chapter outlines biological, methodological and technical issues associated with hypoxia-directed radiation therapy planning with emphasis on their potential application in clinical practice.