Anti-malondialdehyde-modified low-density lipoprotein MDA2 murine monoclonal antibody manganese-micelles

Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally. Protons (hydrogen nuclei) are widely used in imaging because of their abundance in water molecules. Water comprises ~80% of most soft tissue. The contrast of proton MRI depends primarily on the density of the nucleus (proton spins), the relaxation times of the nuclear magnetization (T1, longitudinal; T2, transverse), the magnetic environment of the tissues, and the blood flow to the tissues. However, insufficient contrast between normal and diseased tissues requires the development of contrast agents. Most contrast agents affect the T1 and T2 relaxation times of the surrounding nuclei, mainly the protons of water. T2* is the spin–spin relaxation time composed of variations from molecular interactions and intrinsic magnetic heterogeneities of tissues in the magnetic field (1). Cross-linked iron oxide nanoparticles and other iron oxide formulations affect T2 primarily and lead to decreased signals. On the other hand, paramagnetic T1 agents, such as gadolinium (Gd) and manganese (Mn), accelerate T1 relaxation and lead to brighter contrast images. Apolipoprotein E (apoE) is essential for the normal catabolism of triglyceride-rich lipoprotein chylomicrons (lipoprotein particles) (2). Oxidation of low-density lipoprotein (LDL) generates a number of highly reactive short chain-length aldehydic fragments of oxidized fatty acids capable of conjugating with lysine residues of apoliprotein B and other proteins. Oxidized LDL (OxLDL) is present in atherosclerotic lesions and is essential for the formation of foam cells in atherosclerotic plaques. During atherogenic conditions, deposition of lipids and extracellular matrix proteins on the endothelial cell surfaces of the aorta leads to the development of atherosclerotic plaques (3), which may erode and rupture. MDA2 is a murine monoclonal antibody to malondialdehyde-lysine epitopes of OxLDL and other oxidatively modified proteins, but not to normal LDL (4). The antibody-OxLDL complexes are taken up by macrophages and foam cells in the atherosclerotic plaques. Briley-Saebo et al. (5) demonstrated the accumulation of MDA2 micelles containing Gd (MDA2-Gd micelles) in macrophages of atherosclerotic lesions in apoE-deficient (apoE) mice using MRI. However, Gd may lead to renal toxicity in patients. In another study, Briley-Saebo et al. (6) demonstrated that MDA2-Mn micelles exhibited sensitive and robust detection of atherosclerotic lesions in apoE mice using MRI.