Molecular imaging of VEGF receptors in angiogenic vasculature with single-chain VEGF-based probes.
We describe a new generation of protein-targeted contrast agents for multimodal imaging of the cell-surface receptors for vascular endothelial growth factor (VEGF). These receptors have a key role in angiogenesis and are important targets for drug development. Our probes are based on a single-chain recombinant VEGF expressed with a cysteine-containing tag that allows site-specific labeling with contrast agents for near-infrared fluorescence imaging, single-photon emission computed tomography or positron emission tomography. These probes retain VEGF activities in vitro and undergo selective and highly specific focal uptake into the vasculature of tumors and surrounding host tissue in vivo. The fluorescence contrast agent shows long-term persistence and co-localizes with endothelial cell markers, indicating that internalization is mediated by the receptors. We expect that multimodal imaging of VEGF receptors with these probes will be useful for clinical diagnosis and therapeutic monitoring, and will help to accelerate the development of new angiogenesis-directed drugs and treatments.
Backer
Marina V
MV
SibTech, Inc., 705 North Mountain Road, Newington, Connecticut 06111, USA.
Levashova
Zoya
Z
Patel
Vimalkumar
V
Jehning
Brian T
BT
Claffey
Kevin
K
Blankenberg
Francis G
FG
Backer
Joseph M
JM
D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D003952:Diagnostic Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence / Q000379:methods; D018919:Neovascularization, Physiologic / Q000502:physiology*; D049268:Positron-Emission Tomography / Q000379:methods; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D003287:Contrast Media; D011994:Recombinant Proteins; D040262:Receptors, Vascular Endothelial Growth Factor