Antiangiogenic Cancer Therapy: Monitoring with Molecular US and a Clinically Translatable Contrast Agent (BR55)

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Abstract
Clinically translatable human kinase insert domain receptor–targeted contrast microbubbles can be designed and successfully used for in vivo molecular US of vascular endothelial growth factor receptor 2 in the tumor vasculature in mice. PurposeTo develop and test human kinase insert domain receptor (KDR)-targeted microbubbles (MBs) (MBKDR) for imaging KDR at the molecular level and for monitoring antiangiogenic therapy in a human colon cancer xenograft tumor model in mice.Materials and MethodsAnimal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. A heterodimeric peptide that binds to human KDR with low nanomolar affinity (KD = 0.5 nmol/L) was coupled onto the surface of perfluorobutane-containing lipid-shelled MBs (MBKDR). Binding specificity of MBKDR to human KDR and cross-reactivity with murine vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) were tested in cell culture under flow shear stress conditions (at 100 sec−1). In vivo binding specificity of MBKDR to VEGFR2 was tested in human LS174T colon cancer xenografts in mice with a 40-MHz ultrasonographic (US) transducer. Targeted contrast material–enhanced US imaging signal by using MBKDR was longitudinally measured during 6 days ...