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

Foss CA, Bedja D, Mease RC, Wang H, Kass DA, Chatterjee S, Pomper MG. Biochem Biophys Res Commun. 2015 May 22;461(1):70-5. doi: 10.1016/j.bbrc.2015.03.171. PMID: 25858322

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.