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Abstract #0455

Targeting the Endothelial Cell Surface: Novel Transgenic Mice for Molecular Imaging of Vascular Development

Cesar Augusto Berrios-Otero1, Benjamin B. Bartelle1, Anne E. Friedland1, Daniel H. Turnbull1,2

1Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, United States; 2Department of Radiology, New York University School of Medicine, New York, United States

Paramagnetic contrast agents targeted to cell membrane receptors or other surface proteins are currently of great interest for molecular imaging with MRI. A potential problem with current targeting methods is the limited targeting efficiency, which combined with the low sensitivity of many paramagnetic agents can severely compromise the application of these approaches for in vivo imaging. One way to circumvent problems in targeting contrast agents to surface receptors is to increase the binding affinity of the ligand to its target. An intriguing possibility is to take advantage of the high binding affinity of avidin and biotin. In the current study, transgenic mice expressing an engineered biotin ligase (BirA) and a cluster of biotinylation substrate sequences (Biotags) fused to a transmembrane protein domain were generated. Expression was driven by a minimal Tie2 promoter-enhancer, providing high transgene levels during angiogenesis in developing mouse embryos. Targeting was tested in embryos by means of intracardiac injections of an Avidin-Gd based T1-agent and high resolution 3D T1-weighted imaging.