Noninvasive Vascular Cell Adhesion Molecule-1 Imaging Identifies Inflammatory Activation of Cells in Atherosclerosis
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.
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VCAM1-targeted iron oxides have been developed for early detection of atherosclerotic disease.
“or VCAM1-targeted iron oxides for early detection of atherosclerotic disease47.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [47]
A multimodal nanoparticle has been used to detect plaque inflammation through target-specific imaging of adhesion molecules.
“This is an example of a multimodal nanoparticle being used to detect plaque inflammation via target-specific imaging of adhesion molecules.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [47]
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- Authors
- Nahrendorf, M., Jaffer, F. A., Kelly, K. A., Sosnovik, D. E., Aikawa, E., Libby, P., & Weissleder, R.
- Affiliations
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Circulation
- Published
- 2006-10-03
- Volume
- 114
- Issue
- 14
- Pages
- 1504-1511
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2101037111
- Cited by
- 602
- References
- 42
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 10 · 2023: 12 · 2022: 22 · 2021: 19 · 2020: 17 · 2019: 30 · 2018: 20 · 2017: 22 · 2016: 27 · 2015: 33 · 2014: 51 · 2013: 43 · 2012: 51
- FWCI
- 17.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre d'Imagerie BioMédicale
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital
- National Heart, Lung, and Blood Institute (R01-HL36436, U01HL080731, R01HL078641)
- National Institute of Allergy and Infectious Diseases (P01AI054904)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cerebrovascular and Carotid Artery Diseases
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Keywords
- VCAM-1, atherosclerosis, inflammation, macrophages, endothelial cells, very late antigen-4, ApoE-deficient mice, atorvastatin, carotid plaque, magnetic resonance imaging, optical imaging, subclinical atherosclerosis
- MeSH terms
- Amino Acid Sequence, Animals, Apolipoproteins E, Diagnostic Imaging, Gene Expression Regulation, Inflammation, Ligands, Magnetic Resonance Imaging, Peptides, Down-Regulation, Drug Monitoring, Mice, Knockout, Vascular Cell Adhesion Molecule-1, Atherosclerosis, Mice
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