Molecular Magnetic Resonance and Ultrasound Imaging of Tumor Angiogenesis

Abstract

Seeking out and identifying imaging biomarkers for early cancer diagnosis and the evaluation of patient response to therapy requires an improvement in the specificity of imaging techniques. This study explores in vivo neo-angiogenesis assessment using molecular mechanisms through target molecular Magnetic Resonance (MR) and Ultrasound (US). In this context, our study examines and compares the use of both imaging technics, targeting the same integrin in a mouse xeno graft tumor model. Following xeno transplantation of human renal cell carcinoma (Human A498), thirteen nude mice were injected with ανβ3-targeted and non-targeted Contrast Agents (CA) for MR and US use, respectively. CA binding to the targeted receptor was measured through Dynamic Susceptibility Contrast MR imaging and Differential Targeted Enhancement (DTE) US imaging. The specificities and co location of both targeted CAs were studied throughout the tumor, in both hypo- and hyper-vascularized areas. One hour post injection, a significant difference was observed between the signals of targeted and non-targeted MR CA (p = 0.03). The DTE-US targeted CA was significantly enhanced compared to non-targeted CA (p = 0.002). In the hypo- and hyper-vascularized regions of interest, a strong correlation was observable between both modalities, with values of r10min = 0.86 (p = 0.0003), r30min = 0.85 (p = 0.0004) and r60min = 0.87 (p = 0.0001). This study highlights the specificity of each targeted CA. A high correlation was noted between MR and US molecular imaging for angiogenesis assessment. These two molecular imaging modalities may be used interchangeably to monitor patient response to anti-angiogenic treatment.