Radiotherapy today is well-established for curative as well as palliative treatment of many cancers such as bronchus carcinoma, breast cancer and high grade gliomas. Although substantial progress in the reduction of unnecessary tissue irradiation has been achieved with the introduction of intensity modulated radiotherapy or image-guided radiotherapy, normal tissue adjacent to the target still receives a non-negligible radiation dose leading to corresponding tissue changes such as necrosis, fibrosis and gliosis.
Osteoradionecrosis is a difficult to treat, severe complication after radiation therapy, which implies high health care costs. Early biomarkers are necessary for correct alterations of the treatment plan (medication, operation planning, and stabilization of the vertebral column). Functionally and on a biochemical level the difference between patent tissue and necrosis is enormous e.g. in necrotic areas mobile cytosolic proteins and peptides are absent due to the loss of the cytoplasm. Therefore molecular imaging using MRI with its possibilities for in-vivo tissue characterization – for instance quantifications of relaxation and diffusion properties or magnetization transfer – seems a perfectly suited technique to assess and characterize tissue damage due to radiotherapy. Furthermore osteoradionecrosis leads to changes in the trabecular structure, which is assessable with CT and sophisticated postprocessing methods such as texture analysis. The value of these sophisticated imaging techniques will be examined in a translational mouse model.
The recently acquired high precision small animal irradiation unit at the Department of Radiation Oncology offers the unique possibility to use animal models of radiation injury as well as animal models of cancer treated with radiotherapy. In collaboration with the Institute for Diagnostic and Interventional Radiology we will characterize the MRI and CT properties of osteoradionecrosis after high-dose local radiotherapy using advanced molecular imaging methods in correlation to immunohistochemistry and functional assays. As a result suitable biomarkers shall be identified to allow prediction, detection and monitoring of osteoradionecrosis after radiotherapy.
Molecular imaging techniques used:
Due to the numerous specific properties of tissue regarding magnetic resonance, a comprehensive number of molecular imaging techniques needs to be evaluated including tissue relaxation properties (T1, T2 and T2*), tissue diffusion properties including intra-voxel incoherent motion and diffusion kurtosis imaging techniques as well as magnetization transfer. Micro-CT is used to assess trabecular bone structure directly and via texture analysis.
Added value of KFSP for this specific tandem project:
Bringing together the abilities of the Department of Radiation Oncology and the Institute for Diagnostic and Interventional in a unique preclinical environment allows for systematic evaluation of different approaches using highly specialized techniques in the fields of radiotherapy and molecular imaging.