title: Molecular MRI of atherosclerotic plaque progression in an ApoE(-/-) mouse model with a CLT1 peptide targeted macrocyclic Gd(III) chelate.
abstract: Molecular imaging of atherosclerotic biomarkers is critical for non-invasive detection and diagnosis of atherosclerotic plaques and therapeutic management. Fibrin and fibronectin accumulate at elevated levels in atherosclerotic plaques and are associated with atherogenesis and disease progression. Molecular imaging of these biomarkers has the potential to non-invasively characterize plaque burden. In this work, we investigated the effectiveness of a peptide-targeted macrocyclic Gd(III) chelate, CLT1-dL-(DOTA-Gd)4, specific to fibrin-fibronectin complexes for molecular MRI of atherosclerosis. Atherosclerotic plaques were induced in Apolipoprotein E-knockout (ApoE(-/-)) mice by feeding with high fat and cholesterol-enriched diet (HFD) for up to 30 weeks. MRI of the vessel wall in the arch aorta was performed at 10, 20 and 30 weeks after the onset of HFD. High spatial-resolution MRI was performed prior and up to 35 minutes after i.v. injection of CLT1-dL-(DOTA-Gd)4 or a nonspecific control agent at a dose of 0.1 mmol-Gd/kg. CLT1-dL-(DOTA-Gd)4 produced stronger enhancement in the atherosclerotic lesions of the aortic wall than the control at all time points in the mice. Cross sectional MR images of the aortic arch revealed progressive thickening of the atherosclerotic vessel wall in the mice on HFD for up to 30 weeks. This progression correlated well to histological staining, as well as fibrin and fibronectin immunochemical stained images. Molecular MRI with CLT1-dL-(DOTA-Gd)4 has a potential for detecting atherosclerosis and non-invasive monitoring of the progression of the plaques.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Cleveland, OH 44106, USA.
authors.forename: Xueming
authors.initials: X
authors.lastname: Wu
authors.forename: Niranjan
authors.initials: N
authors.lastname: Balu
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Shi
authors.forename: China M
authors.initials: CM
authors.lastname: Kummitha
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.forename: Chun
authors.initials: C
authors.lastname: Yuan
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Lu
keywords: CLT1 peptide; Molecular MRI; atherosclerosis; macrocyclic Gd(III) chelate; targeted contrast agent