Catherine A Foss1, Djahida Bedja2, Ronnie C Mease3, Haofan Wang3, David A Kass4, Subroto Chatterjee5, Martin G Pomper3. 1. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: cfoss1@jhmi.edu. 2. Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia. 3. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. 4. Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. 5. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
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, [(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.
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, [(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.
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