Imaging of Atherosclerosis In Vivo Using a Magnetic Resonance Contrast Probe Molecularly Targeted to Matrix Metalloproteinases (MMPs).
Vucic E, Hyafil F, Lancelot E, Mani V, Corot C, Fayad Z, Amirbekian S, Aguinaldo J, Amirbekian V, Sirol M
Mount Sinai School of Medicine
We tested the in-vivo ability of P947 to detect and assess atherosclerosis using molecular MRI. P947 contains a ligand to matrix-metalloproteinases (MMPs) that is attached to a gadolinium-chelate making it into a molecular MRI contrast-agent. MMPs play a very important role in atherosclerosis plaque progression and rupture leading to thrombosis. Our results show that compared to several controls, including a scrambled version of P947(P1135), P947 facilitated excellent enhancement of atherosclerosis in ApoE-knockout mice. P947 provided a 125% normalized increase in signal-intensity of atherosclerotic vessels compared to controls. The results were corroborated using pathology, MMP immunohistochemistry techniques and MMP zymography methods.