Detection of tumor angiogenesis in vivo by αvβ3-targeted magnetic resonance imaging

Angiogenesis, the formation of new blood vessels, is a requirement for malignant tumor growth and metastasis(1-3). In the absence of angiogenesis, local tumor expansion is suppressed at a few millimeters and cells lack routes for distant hematogenous spread. Clinical studies have demonstrated that the degree of angiogenesis is correlated with the malignant potential of several cancers, including breast cancer and malignant melanoma(4-7). Moreover, the expression of a specific angiogenesis marker, the endothelial integrin alpha(nu)beta(3), has been shown to correlate with tumor grade(8-10). However, studies of tumor angiogenesis such as these have generally relied on invasive procedures, adequate tissue sampling and meticulous estimation of histologic microvessel density. In the present report, we describe a novel approach to detecting angiogenesis in vivo using magnetic resonance imaging (MRI) and a paramagnetic contrast agent targeted to endothelial alpha(nu)beta(3), via the LM609 monoclonal antibody(11). This approach provided enhanced and detailed imaging of rabbit carcinomas by directly targeting paramagnetic agents to the angiogenic vasculature. In addition, angiogenic 'hot spots' not seen by standard MRI were detected. Our strategy for MR imaging of alpha(nu)beta(3) thus represents a non-invasive means to assess the growth and malignant phenotype of tumors.