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.