Angiogenesis is an essential feature of
cancer growth and
metastasis formation. In bone
metastasis, angiogenic factors are pivotal for
tumor cell proliferation in the bone marrow cavity as well as for interaction of
tumor and bone cells resulting in local bone destruction. Our aim was to develop a model of experimental bone
metastasis that allows in vivo assessment of angiogenesis in skeletal lesions using non-invasive imaging techniques. For this purpose, we injected 10(5) MDA-MB-231 human
breast cancer cells into the superficial epigastric artery, which precludes the growth of
metastases in body areas other than the respective hind leg. Following 25-30 days after
tumor cell inoculation, site-specific bone
metastases develop, restricted to the distal femur, proximal tibia and proximal fibula. Morphological and functional aspects of angiogenesis can be investigated longitudinally in bone
metastases using magnetic resonance imaging (MRI), volumetric computed tomography (VCT) and ultrasound (US). MRI displays morphologic information on the soft tissue part of bone
metastases that is initially confined to the bone marrow cavity and subsequently exceeds cortical bone while progressing. Using dynamic contrast-enhanced MRI (DCE-MRI) functional data including regional blood volume, perfusion and vessel permeability can be obtained and quantified. Bone destruction is captured in high resolution using morphological VCT imaging. Complementary to MRI findings, osteolytic lesions can be located adjacent to sites of intramedullary
tumor growth. After
contrast agent application, VCT angiography reveals the macrovessel architecture in bone
metastases in high resolution, and DCE-VCT enables insight in the microcirculation of these lesions. US is applicable to assess morphological and functional features from skeletal lesions due to local
osteolysis of cortical bone. Using B-mode and Doppler techniques, structure and perfusion of the soft tissue
metastases can be evaluated, respectively. DCE-US allows for real-time imaging of vascularization in bone
metastases after injection of
microbubbles. In conclusion, in a model of site-specific
breast cancer bone
metastases multi-modal imaging techniques including MRI, VCT and US offer complementary information on morphology and functional parameters of angiogenesis in these skeletal lesions.