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.