In vivo phage display selection yields atherosclerotic plaque targeted peptides for imaging.
OBJECTIVE
Atherosclerosis is a leading cause of morbidity and mortality in the Western world, yet specific imaging agents to detect and map inflammatory plaques are still lacking.


METHODS
We used in vivo phage display to interrogate early atherosclerotic lesions present in ApoE-/- mice with the goal of identifying plaque-associated endothelial cell internalized affinity ligands.


RESULTS
We identified 30 phage families with some of these families exhibiting homology to known atherosclerotic proteins, namely, leukemia inhibitory factor, transferrin, and VLA-4. VLA-4 homologous peptides [termed vascular cellular adhesion molecule-1 (VCAM-1) internalizing peptide-28 (VINP28)] bound to and were internalized by VCAM-1-expressing cells and were inhibited by soluble VCAM-1. In addition, a VINP28 modified multimodal nanoparticle showed high affinity for endothelial cells expressing VCAM-1 but low affinity for macrophages or smooth muscle cells.


CONCLUSIONS
The identified peptides represent a set of probes to interrogate the cell surface repertoire and potentially allow early detection of atherosclerosis.
Kelly
Kimberly A
KA
Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, 149, 13th Street, Rm 5404, Charlestown, MA 02129, USA.
Nahrendorf
Matthias
M
Yu
Amy M
AM
Reynolds
Fred
F
Weissleder
Ralph
R
D000345:Affinity Labels; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000175:diagnosis*; D016893:Carotid Stenosis / Q000175:diagnosis*; D002478:Cells, Cultured; D042783:Endothelial Cells; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008280:Magnetics; D051379:Mice; D008817:Mice, Mutant Strains; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000166:cytology; D049329:Nanostructures; D019151:Peptide Library; D018121:Receptors, Cytokine / Q000378:metabolism; D053606:Receptors, OSM-LIF; D011990:Receptors, Transferrin / Q000378:metabolism; D012307:Risk Factors; D017386:Sequence Homology, Amino Acid; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000345:Affinity Labels; D001057:Apolipoproteins E; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507841:Lifr protein, mouse; D019151:Peptide Library; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D011990:Receptors, Transferrin; D019010:Vascular Cell Adhesion Molecule-1