DCE-MRI in assessment of tumor hypoxia, radiation response, and metastatic potential
Appears in the following Collection
- Fysisk institutt 
AbstractHypoxia in tumors has been found to decrease the effectiveness of cancer treatment; in particular, it can diminish the effect of radiation therapy. Furthermore, hypoxia has been associated with malignant progression and metastatic disease. Patients with hypoxic tumors may thus benefit from a more aggressive treatment. A noninvasive diagnostic method for detecting these tumors is therefore urgently needed. In this thesis, the potential usefulness of dynamic Gd-DTPA-enhanced MRI for assessing tumor hypoxia, radiation response, and metastatic potential has been evaluated preclinically. The DCE-MRI series were analyzed by using one of the most widely known pharmacokinetic models, the generalized kinetic model of Tofts. Human melanoma xenografts and cervical carcinoma xenografts were used as tumor models in the study. The DCE-MRI-derived parameters Ktrans and νe values were shown to be able to distinguish between tumors with and without hypoxia, as well as to give information about the extent of tumor hypoxia. Furthermore, it was demonstrated that Ktrans is able to predict radiation response. Finally, both Ktrans and νe showed the ability to predict metastatic potential. In conclusion, this preclinical study demonstrates the potential of the DCE-MRI-derived parameters Ktrans and νe as predictive markers, warranting further clinical studies.
List of papers. The papers are removed from the thesis due to copyright restrictions.
Paper I Ellingsen, C., Øvrebø, K.M., Galappathi, K., Mathiesen, B., and Rofstad, E.K. (2012). The pO2 fluctuation pattern and cycling hypoxia in human cervical carcinoma and melanoma xenografts. Int. J. Radiat. Oncol. Biol. Phys. 83, 1317-1323. doi:10.1016/j.ijrobp.2011.09.037
Paper II Gulliksrud, K., Øvrebø, K.M., Mathiesen, B., Rofstad, E.K. (2011). Differentiation between hypoxic and non-hypoxic experimental tumors by dynamic contrastenhanced magnetic resonance imaging. Radiother. Oncol. 98, 360-364. doi:10.1016/j.radonc.2010.12.016
Paper III Øvrebø, K.M., Hompland, T., Mathiesen, B., and Rofstad, E.K. (2012). Assessment of hypoxia and radiation response in intramuscular experimental tumors by dynamic contrast-enhanced magnetic resonance imaging. Radiother. Oncol. 102, 429-435. doi:10.1016/j.radonc.2011.11.013
Paper IV Øvrebø, K.M., Gulliksrud, K., Mathiesen, B., and Rofstad, E.K. (2011). Assessment of tumor responsiveness and metastatic potential by dynamic contrast-enhanced magnetic resonance imaging. Int. J. Radiat. Oncol. Biol. Phys. 81, 255-261. doi:10.1016/j.ijrobp.2011.04.008
Paper V Øvrebø, K.M., Ellingsen, C., Hompland, T., and Rofstad, E.K. (2012). Dynamic contrast-enhanced magnetic resonance imaging of the metastatic potential of tumors: A preclinical study of cervical carcinoma and melanoma xenografts. Acta Oncologica. Posted online on June 7, 2012. doi:10.3109/0284186X.2012.689851
Paper VI Øvrebø, K.M., Ellingsen, C., Galappathi, K., and Rofstad E.K. (2012). Dynamic contrast-enhanced magnetic resonance imaging of the metastatic potential of human melanoma xenografts. Int. J. Radiat. Oncol. Biol. Phys. 83, e121-e127. doi:10.1016/j.ijrobp.2011.12.019