Determination of the dynamics of tumor hypoxia during radiation therapy using biological imaging on mouse xenograft tumors

Background: Chronic, acute and hypoxemic hypoxia can lead to resistance to radiation therapy. The purpose of this thesis was to shed light on the role of these three hypoxia subtypes in radiotherapy. Methods: The amount of total hypoxia and hypoxia subtypes were assessed ex-vivo in xenograft tumors via (immuno-)fluorescence and H&E staining. For the non-invasive detection of hypoxia, tumor-bearing mice were injected with 18F-FMISO and underwent a dynamic PET/CT scan. The hypoxic fraction was quantified using the mathematical Wang Model. Results and Conclusions: Total hypoxia was non-homogeneously distributed from the apical to the basal part of the tumors. Chronic hypoxia was the most abundant subtype before and after irradiation, followed by acute and hypoxemic hypoxia. Based on 18F-FMISO PET/CT measurements the Wang Model can be applied for the quantification of acute and chronic hypoxia. However, further preclinical investigations are required before implementation in the clinic.