Abstract 5790: Dual Molecular Imaging for Assessment of Matrix Metalloproteinase and Apoptosis in Atherosclerotic Lesions before and after Statin Therapy
We evaluated the correlation between matrix metalloproteinase (MMP) and apoptotic activities in atherosclerosis lesions, and the impact of lipid lowering by dietary modification and statin therapy employing molecular imaging with Tc-99m broad MMP inhibitor (MPI) and indium-111 annexin A5 (AA5). Atherosclerosis was produced in 13 New Zealand White rabbits by balloon deendothelialization and hypercholesterolemic diet for 4 months; 6 unmanipulated rabbits on normal chow were used as controls. In the last month, 3 of the 13 atherosclerotic rabbits were changed to normal chow, and 4 received fluvastatin (1mg/kg) once a day. MPI and AA5 imaging were performed using micro-SPECT/micro-CT. After in vivo imaging, aortas were explanted to acquire ex vivo images and calculate percent injected dose per gram (%ID/g) uptake. Histological and immunohistochemical characterization and extent of MMP and apoptosis were evaluated in representative aortic samples. Both MPI and Annexin uptake were clearly visualized in the atherosclerotic lesions by noninvasive imaging; No uptake were observed after diet withdrawal, fluvastatin, and in normal control groups. %ID/g MPI and AA5 uptakes in the atherosclerotic lesions (0.09 ± 0.02%, 0.03 ± 0.01%) were significantly higher than the uptake in control abdominal aorta (0.014 ± 0.004%, 0.0007 ± 0.0002%; p<0.0001). The quantitative uptake in fluvastatin (0.053 ± 0.013%, 0.02 ± 0.01%; p<0.05) and diet withdrawal (0.047 ± 0.005%, 0.02 ± 0.004%; p<0.05) groups were statistically significantly lower compared to diet uninterrupted group. There were significant direct relationship betweem MPI and AA5 uptake in all experimental group (r=0.62, p<0.0001). The decrease in the tracer uptake maintained the relationship in the fluvastatin group (r=0.62, p<0.0001) but became less apparent in the diet withdrawal (r=0.24, p<0.05). Histopathological and immunohisto-chemical studies revealed a significant correlation of both MPI and Annexin uptake with macrophage infiltration, MMP-2, 9 expression and the extent of apoptosis. Dual imaging with MPI and AA5 showed good correlation between apoptosis and MMP expression except diet withdrawal group.