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, [125I]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.

Perilipin 5 deficiency promotes atherosclerosis progression through accelerating inflammation, apoptosis, and oxidative stress

“…ApoE −/− mouse model was chosen to explore atherosclerosis because it is a well-established animal model where all recognized stages of atherogenesis could be observed. [11][12][13] Moreover, the complexity and morphological characteristics of atherosclerotic lesions developing in the animal model are very close to those in human. 14 In ApoE −/− mice, atherosclerosis is driven by the impaired clearance of cholesterol-enriched lipoproteins, leading to elevated levels of atherogenic remnants and plasma cholesterol.…”

“…Mice lacking Apolipoprotein E (ApoE) can develop hypercholesterolaemia and atherosclerosis, more pronouncedly under the induction of high‐fat diet. ApoE −/− mouse model was chosen to explore atherosclerosis because it is a well‐established animal model where all recognized stages of atherogenesis could be observed . Moreover, the complexity and morphological characteristics of atherosclerotic lesions developing in the animal model are very close to those in human .…”

Molecular Imaging of Inflammation: Current Status

“…In one study, 18 F-FDG uptake was found to correlate positively with macrophage density (23). TSPO ligands such as 125 I-DPA-713 (N,N-diethyl-2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide) (24) and 11 C-PK11195 (25), as well as labeled DOTATATE ( 68 Ga and 64 Cu) (Fig. 3) (26), have also been used in the evaluation of plaques.…”

Cardiovascular Imaging in Mice

“…Atherosclerotic lesions, an abnormally thickened intima-media layer, and vascular thromboses may be directly imaged with high resolution ultrasound (Choudhury et al, 2004; Chatterjee et al, 2014; Zhang et al, 2015) and also enhanced with specific contrast agents (Wang et al, 2012; Foss et al, 2015). Arterial stiffness may be determined by the pulse wave velocity (Hartley et al, 2011; Chatterjee et al, 2014) or a combination of aortic diameter and invasive blood pressure measurements (Kuo et al, 2014); for a more precise determination of localized arterial wall characteristics, pulse wave imaging has more recently been developed (Fujikura et al, 2007; Nandlall et al, 2014).…”