Objective-Labeled oxidation-specific antibodies (Ox-AB) detect, quantify, and noninvasively image lipid-rich atherosclerotic lesions. However, it is unknown whether Ox-AB detect plaque stabilization. Methods and Results-The aortic uptake of intravenously injected 125 I-MDA2 (Ox-AB to malondialdehyde [MDA]-lowdensity lipoprotein [LDL]) was quantitated in: (1) LDL receptorϪ/Ϫ mice with established atherosclerosis continued on Western diet (Progression) or switched to chow (Regression) or chowϩvitamins E and C (Regression-VIT) for 6 months; and (2) Watanabe rabbits (3-to 57-months old) with naturally evolved atherosclerotic lesions. In mice, the Progression group had more extensive atherosclerosis, higher 125 I-MDA2 uptake, high concordance of Sudan (lipid)-staining and 125 I-MDA2 uptake, and stronger oxidized LDL (OxLDL) and macrophage immunostaining than both Regression groups. In contrast, the Regression groups showed Sudan-positive lesions with focally diminished 125 I-MDA2 uptake, which coincided with reduced OxLDL and macrophages but more smooth muscle cells (SMCs) and collagen. In rabbits, areas of increased 125 I-MDA2 uptake were associated with high Sudan concordance and strong immunostaining for OxLDL and macrophages. Interestingly, advanced lesions with focally diminished 125 I-MDA2 uptake showed stronger immunostaining for SMCs and collagen, particularly at the fibrous cap. Several invasive and noninvasive techniques are being intensively evaluated for detection of such plaques. 5 OxLDL and oxidation-specific epitopes, which are relatively accessible targets, particularly when present in the form of large extracellular deposits in the lipid core, 6 -8 are rational targets for imaging and may serve as markers of plaque vulnerability.
Conclusion-Ox-AB
See page 2203We have shown previously that intravenously injected, radiolabeled oxidation-specific antibodies (Ox-AB), such as the murine monoclonal antibody (MAB) MDA2, which detects malondialdehyde (MDA)-lysine epitopes, have a strong and specific predilection for atherosclerotic lesions but not normal arteries. 9,10 Aortic uptake of 125 I-MDA2 is enhanced in lipid-rich lesions and reduced in lesions of LDL receptorϪ/Ϫ (LDLRϪ/Ϫ) mice on dietary/antioxidant diets. 10 99m Tc-labeled MDA2 noninvasively images atherosclerotic lesions in live animals. 9 However, it is unknown whether plaque uptake of radiolabeled Ox-AB may reflect the changes that occur when plaques become more stable, a property that would potentially enhance the utility of this imaging approach in patients at risk for plaque rupture. The present study therefore assessed the rela-