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Title: Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA

Abstract

Background: Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis. Methods and results: We previously developed a low-molecular-weight imaging agent, [{sup 125}I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE -/- mouse model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE -/- mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals. Conclusions: IodoDPA is a promising new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved. - Highlights: • [{sup 125}I]iodoDPA SPECT detects atherosclerotic plaques in ApoE -/- mice with high contrast. •more » Plaques are detected in ApoE -/- mice regardless of diet with iodoDPA. • iodoDPA has very low uptake in healthy tissue including healthy TSPO + tissues at 24 h.« less

Authors:
 [1];  [2];  [3]; ;  [1];  [2];  [4];  [1]
  1. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States)
  2. Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States)
  3. (Australia)
  4. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States)
Publication Date:
OSTI Identifier:
22462052
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 461; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; AORTA; ARTERIOSCLEROSIS; BIOMEDICAL RADIOGRAPHY; CAROTID ARTERIES; CORONARIES; DIET; FATS; FLUORESCENCE; HISTOLOGY; INFLAMMATION; IODINE 125; MACROPHAGES; MICE; MYOCARDIAL INFARCTION; SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY; SPECIFICITY; TRACER TECHNIQUES; UPTAKE

Citation Formats

Foss, Catherine A., E-mail: cfoss1@jhmi.edu, Bedja, Djahida, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Mease, Ronnie C., Wang, Haofan, Kass, David A., Chatterjee, Subroto, and Pomper, Martin G. Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.03.171.
Foss, Catherine A., E-mail: cfoss1@jhmi.edu, Bedja, Djahida, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Mease, Ronnie C., Wang, Haofan, Kass, David A., Chatterjee, Subroto, & Pomper, Martin G. Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA. United States. doi:10.1016/J.BBRC.2015.03.171.
Foss, Catherine A., E-mail: cfoss1@jhmi.edu, Bedja, Djahida, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Mease, Ronnie C., Wang, Haofan, Kass, David A., Chatterjee, Subroto, and Pomper, Martin G. Fri . "Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA". United States. doi:10.1016/J.BBRC.2015.03.171.
@article{osti_22462052,
title = {Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA},
author = {Foss, Catherine A., E-mail: cfoss1@jhmi.edu and Bedja, Djahida and Faculty of Medicine and Health Sciences, Macquarie University, Sydney and Mease, Ronnie C. and Wang, Haofan and Kass, David A. and Chatterjee, Subroto and Pomper, Martin G.},
abstractNote = {Background: Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis. Methods and results: We previously developed a low-molecular-weight imaging agent, [{sup 125}I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE -/- mouse model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE -/- mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals. Conclusions: IodoDPA is a promising new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved. - Highlights: • [{sup 125}I]iodoDPA SPECT detects atherosclerotic plaques in ApoE -/- mice with high contrast. • Plaques are detected in ApoE -/- mice regardless of diet with iodoDPA. • iodoDPA has very low uptake in healthy tissue including healthy TSPO + tissues at 24 h.},
doi = {10.1016/J.BBRC.2015.03.171},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 461,
place = {United States},
year = {2015},
month = {5}
}