Foss Catherine A, Bedja Djahida, Mease Ronnie C, Wang Haofan, Kass David A, Chatterjee Subroto, Pomper Martin G
Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
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.
Biochem Biophys Res Commun. 2015 May 22;461(1):70-5. doi: 10.1016/j.bbrc.2015.03.171. Epub 2015 Apr 6.
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.
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.
IodoDPA is a promising new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved.
动脉粥样硬化是一种常见且严重的血管疾病,使个体易患心肌梗死和中风。血管内斑块是动脉粥样硬化的病理病变,主要由富含胆固醇的管腔巨噬细胞浸润组成,位于纤维帽内。能够在主动脉、颈动脉和其他血管内非侵入性地检测这些巨噬细胞,将使医生能够确定斑块负荷,有助于动脉粥样硬化患者的管理。
我们之前开发了一种低分子量成像剂[(125)I]碘代-DPA-713(碘代DPA),它能选择性地靶向巨噬细胞。在此,我们使用它通过单光子发射计算机断层扫描(SPECT)在动脉粥样硬化的ApoE -/-小鼠模型中检测血管内巨噬细胞和心肌内的巨噬细胞浸润。SPECT数据通过超声心动图、近红外荧光成像和组织学得到证实。SPECT图像显示所有ApoE -/-小鼠的主动脉根部有放射性示踪剂的局灶性摄取,而年龄匹配的对照组几乎没有放射性示踪剂摄取。在受影响的动物中还观察到沿降主动脉和心肌内有局灶性放射性示踪剂摄取。
碘代DPA是一种有前景的用于动脉粥样硬化的新型成像剂,对所涉及病变的巨噬细胞成分具有特异性。