文章基本信息

标题：SPECT/CT Imaging of High-Risk Atherosclerotic Plaques using Integrin-Binding RGD Dimer Peptides
本地全文：下载
作者：Jung Sun Yoo ; Jonghwan Lee ; Jae Ho Jung 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
DOI：10.1038/srep11752
出版社：Springer Nature
摘要：Vulnerable atherosclerotic plaques with unique biological signatures are responsible for most major cardiovascular events including acute myocardial infarction and stroke. However, current clinical diagnostic approaches for atherosclerosis focus on anatomical measurements such as the degree of luminal stenosis and wall thickness. An abundance of neovessels with elevated expression of integrin α_vβ₃ is closely associated with an increased risk of plaque rupture. Herein we evaluated the potential of an α_vβ₃ integrin-targeting radiotracer, ^99mTc-IDA-D-[c(RGDfK)]₂, for SPECT/CT imaging of high-risk plaque in murine atherosclerosis models. In vivo uptake of ^99mTc-IDA-D-[c(RGDfK)]₂ was significantly higher in atherosclerotic aortas than in relatively normal aortas. Comparison with the negative-control peptide, ^99mTc-IDA-D-[c(RADfK)]₂, proved specific binding of ^99mTc-IDA-D-[c(RGDfK)]₂ for plaque lesions in in vivo SPECT/CT and ex vivo autoradiographic imaging. Histopathological characterization revealed that a prominent SPECT signal of ^99mTc-IDA-D-[c(RGDfK)]₂ corresponded to the presence of high-risk plaques with a large necrotic core, a thin fibrous cap, and vibrant neoangiogenic events. Notably, the RGD dimer based ^99mTc-IDA-D-[c(RGDfK)]₂ showed better imaging performance in comparison with the common monomeric RGD peptide probe ¹²³I-c(RGDyV) and fluorescence tissue assay corroborated this. Our preclinical data demonstrated that ^99mTc-IDA-D-[c(RGDfK)]₂ SPECT/CT is a sensitive tool to noninvasively gauge atherosclerosis beyond vascular anatomy by assessing culprit plaque neovascularization.