Abstract 2434: Noninvasive Monitoring of Atherosclerotic Plaque with Radiolabeled Annexin V and Matrix Metalloproteinase Inhibitor in Spontaneous Atherosclerotic Mice
Introduction: Vascular apoptosis and extracellular matrix degradation render atherosclerotic plaques vulnerable to rupture. We assessed the hypothesis that molecular imaging can be used as a noninvasive tool to access lesion pathology in apolipoprotein E deficient (apoE−/ −) mice using either 99mTc-broad-based matrix metalloproteinase inhibitor (MPI) or 99mTc-annexin V.
Methods: Twenty-one apoE−/ − mice were studied. At six wk of age and while on a chow diet, mice underwent baseline planar gamma imaging 2 hr post tail vein injection of 5.4 –7.2 MBq 99mTc-Annexin V and 48 hr later with 99mTc-MPI. Mice were then fed a high-cholesterol diet and injected and imaged with alternating tracer sequence at 9, 15, and 20 wk and sacrificed at each time point. The hearts and aortas were explanted for ex-vivo well counting and histology.
Results: No scans were positive at 6 or 9 wk. Six out of 11 (15 and 20 wk) mice were scan positive for 99mTc-Annexin V and 2 for 99mTc-MPI and annexin V. See table⇓ for mean values. Scan (+) for MPI and annexin V showed type III-IV lesions with (+) MMPs, (+) caspase, and (+) macrophages. Scan (+) for annexin V and (−) for MPI showed type II-III with mostly smooth muscle cells, (+) caspase, (−) MMPs. Scan (−) for both showed type II lesions with (−) caspase and (−) MMPs.
Conclusion: These data suggest that 99mTc-Hynic-Annexin V and 99mTc-MPI can be used to noninvasively identify lesion severity.