Non-Invasive Assessment of Vascular Changes in an Animal Model of Breast Cancer Bone Metastases After Treatment with an Integrin Antagonist Using DCE-MRI

Dorde Komljenovic¹, Maximilian Merz¹, Wolfhard Semmler¹, Tobias Buerle¹

Breast cancer frequently metastasizes to the skeleton, resulting in predominantly osteolytic lesions causing pain and fracture. In bone metastases, αvβ3 integrin is significantly up-regulated on activated endothelial cells and recognized as an important factor in bone resorption. Furthermore, αvβ5 integrin is expressed on various breast cancer cells, including the human breast cancer cell line MDA-MB-231. In this study, we have investigated effects of the inhibition of αvβ3 and αvβ5 integrins in bone metastases by employing a small molecule antagonist of this integrin subclass. Further, our aim was to elucidate whether therapeutic effects, visualized and quantified using dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) and flat panel volumetric computed tomography (VCT), allow early prediction of treatment response in experimental breast cancer bone metastases.