Abstract 2615: In vivo Monitoring of Matrix Metalloproteinase Activity with P947-Enhanced MRI in Atherosclerotic Plaques of Hypercholesterolemic Rabbits
Introduction. Matrix metalloproteinases (MMPs) are involved in atherosclerotic plaque growth and rupture. P947 (Guerbet) is a new MRI contrast agent formed of a peptide with a high affinity for MMPs, bound to a molecule of gadolinium chelate (molecular weight: 1210 Daltons; R1 = 5.5 s−1mM−1 at 1.5 Tesla).
Hypothesis. Our hypothesis was to assess whether MMP activity can be monitored in atherosclerotic plaques of hypercholesterolemic rabbits with P947-enhanced MRI.
Methods. Atherosclerotic plaques were induced in the aorta of 8 New-Zealand White rabbits by double balloon injury (4 weeks apart) and 4 months hypercholesterolemic diet. At that time, a T1-weighted MRI of the aorta was acquired in 8 rabbits before and 90 minutes after intravenous injection of 50 μM Gd/kg of P947. One week later, the same rabbits were imaged after injection of 50 μM Gd/kg of a conventional MRI contrast agent (Gd-DOTA). After this first imaging session, 4 rabbits were maintained on a hypercholesterolemic diet (“progression” group) and 4 rabbits were switched to a chow diet (“regression” group). A second imaging session was performed 4 months later in both groups using the same imaging protocol as for the first imaging time point. On each MRI acquisition, signal intensities were measured in atherosclerotic plaques.
Results. On the first P947-enhanced MRI, signal intensities of atherosclerotic plaques increased similarly in rabbits from the “progression” group (36 ± 3 %) and from the “regression group” (41 ± 5 %). On the second P947-enhanced MRI, signal enhancement in atherosclerotic plaques from the “progression” group was similar to the first MRI (38 ± 2 %; p = NS vs. first MRI), while a significantly lower enhancement was found in the “regression group” (14 ± 3 %; p = 0.05 vs. first MRI). No significant difference in MR signal intensity was found in atherosclerotic plaques after injection of Gd-DOTA.
Conclusion. P947-enhanced MRI allows the monitoring of MMP activity in atherosclerotic plaques of hypercholesterolemic rabbits. This technique is promising for the detection of vulnerable atherosclerotic plaques with MRI and to monitor the efficacy of therapies aimed at plaque stabilization.