DOI: 10.1161/circulationaha.106.646380. Noninvasive Vascular Cell Adhesion Molecule-1 Imaging Identifies Inflammatory Activation of Cells in Atherosclerosis

Noninvasive Vascular Cell Adhesion Molecule-1 Imaging Identifies Inflammatory Activation of Cells in Atherosclerosis

10.1161/circulationaha.106.646380

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Circulation (276)

Abstract

Background— Noninvasive imaging of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) may identify early stages of inflammation in atherosclerosis. We hypothesized that a novel, second-generation VCAM-1–targeted agent with enhanced affinity had sufficient sensitivity to enable real-time detection of VCAM-1 expression in experimental atherosclerosis in vivo, to quantify pharmacotherapy-induced reductions in VCAM-1 expression, and to identify activated cells in human plaques. Methods and Results— In vivo phage display in apolipoprotein E–deficient mice identified a linear peptide affinity ligand, VHPKQHR, homologous to very late antigen-4, a known ligand for VCAM-1. This peptide was developed into a multivalent agent detectable by MRI and optical imaging (denoted VINP-28 for VCAM-1 internalizing nanoparticle 28, with 20 times higher affinity than previously reported for VNP). In vitro, VINP-28 targeted all cell types expressing VCAM-1. In vivo, MRI and optical imaging in apolipoprotein E–deficient mice (n=28) after injection with VINP-28 or saline revealed signal enhancement in the aortic root of mice receiving VINP-28 ( P <0.05). VINP-28 colocalized with endothelial cells and other VCAM-1–expressing cells, eg, macrophages, and was spatially distinct compared with untargeted control nanoparticles. Atheromata of atorvastatin-treated mice showed reduced VINP-28 deposition and VCAM-1 expression. VINP-28 enhanced early lesions in juvenile mice and resected human carotid artery plaques. Conclusions— VINP-28 allows noninvasive imaging of VCAM-1–expressing endothelial cells and macrophages in atherosclerosis and spatial monitoring of anti–VCAM-1 pharmacotherapy in vivo and identifies inflammatory cells in human atheromata. This clinically translatable agent could noninvasively detect inflammation in early, subclinical atherosclerosis.

Bibliography

Nahrendorf, M., Jaffer, F. A., Kelly, K. A., Sosnovik, D. E., Aikawa, E., Libby, P., & Weissleder, R. (2006). Noninvasive Vascular Cell Adhesion Molecule-1 Imaging Identifies Inflammatory Activation of Cells in Atherosclerosis. Circulation, 114(14), 1504â1511.

Authors 7

Matthias Nahrendorf (first)
Farouc A. Jaffer (additional)
Kimberly A. Kelly (additional)
David E. Sosnovik (additional)
Elena Aikawa (additional)
Peter Libby (additional)
Ralph Weissleder (additional)

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Dates

Type	When
Created	18 years, 11 months ago (Sept. 25, 2006, 9:03 p.m.)
Deposited	1 year, 3 months ago (May 13, 2024, 12:29 a.m.)
Indexed	1 week, 1 day ago (Aug. 29, 2025, 6:20 a.m.)
Issued	18 years, 11 months ago (Oct. 3, 2006)
Published	18 years, 11 months ago (Oct. 3, 2006)
Published Print	18 years, 11 months ago (Oct. 3, 2006)

Funders 0

None

BibTeX

@article{Nahrendorf_2006, title={Noninvasive Vascular Cell Adhesion Molecule-1 Imaging Identifies Inflammatory Activation of Cells in Atherosclerosis}, volume={114}, ISSN={1524-4539}, url={http://dx.doi.org/10.1161/circulationaha.106.646380}, DOI={10.1161/circulationaha.106.646380}, number={14}, journal={Circulation}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Nahrendorf, Matthias and Jaffer, Farouc A. and Kelly, Kimberly A. and Sosnovik, David E. and Aikawa, Elena and Libby, Peter and Weissleder, Ralph}, year={2006}, month=oct, pages={1504–1511} }

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