Multimodal Imaging of Pathophysiological Changes and Their Role in Development of Breast Cancer Brain Metastasis.

摘要

Brain metastasis represents a poor prognosis and is frequently the cause of death in breast cancer patients. Tumor microcirculation and oxygenation play important roles in malignant progression and metastasis, as well as response to various therapies. Understanding of hypoxia development and its relationship with blood brain barrier (BBB) during intracranial tumor growth will be crucial for clinical management of breast cancer brain metastasis. We have developed a MRI approach based on an interleaved T2*- and T1-weighted MRI sequence, which will provide information of both tumor vascular and tissue oxygenation. Moreover, by introducing hypoxia reporter gene (HRE- luciferase) into breast tumor lines, we will be able to use bioluminescence imaging to monitor hypoxia initiation and development of intracranial tumors. We will also correlate BBB function based on dynamic contrast enhanced (DCE) MRI with tumor hypoxia. We believe that integration of MRI and BLI will provide temporal and spatial information of tumor hypoxia evolution. Tumor hypoxia leads to resistance to anticancer therapies, in particular radiation, which is perhaps the most important treatment modality in our current armamentarium for brain metastasis. A combination of radiation with hypoxia modifier, 2- methoxyestradiol, on brain metastases will be evaluated by in vivo imaging.