Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
Bioconjug Chem. 2009 May 20;20(5):937-43. doi: 10.1021/bc800520d.
Determining arterial macrophage expression is an important goal in the molecular imaging of atherosclerosis. Here, we compare the efficacy of two synthetic, high density lipoprotein (HDL) based contrast agents for magnetic resonance imaging (MRI) of macrophage burden. Each form of HDL was labeled with gadolinium and rhodamine to allow MRI and fluorescence microscopy. Either the 37 or 18 amino acid peptide replaced the apolipoprotein A-I in these agents, which were termed 37pA-Gd or 18A-Gd. The diameters of 37pA-Gd and 18A-Gd are 7.6 and 8.0 nm, respectively, while the longitudinal relaxivities are 9.8 and 10.0 (mM s)(-1). 37pA has better lipid binding properties. In vitro tests with J774A.1 macrophages proved the particles possessed the functionality of HDL by eliciting cholesterol efflux and were taken up in a receptor-like fashion by the cells. Both agents produced enhancements in atherosclerotic plaques of apolipoprotein E knockout mice of approximately 90% (n = 7 per agent) and are macrophage specific as evidenced by confocal microscopy on aortic sections. The half-lives of 37pA-Gd and 18A-Gd are 2.6 and 2.1 h, respectively. Despite the more favorable lipid interactions of 37pA, both agents gave similar, excellent contrast for the detection of atherosclerotic macrophages using MRI.
确定动脉巨噬细胞的表达是动脉粥样硬化分子成像的重要目标。在这里，我们比较了两种合成的高密度脂蛋白（HDL）基对比剂在磁共振成像（MRI）检测巨噬细胞负荷中的效果。这两种形式的 HDL 都用钆和罗丹明标记，以便进行 MRI 和荧光显微镜检查。这些试剂中的载脂蛋白 A-I 分别被 37 个或 18 个氨基酸肽取代，分别称为 37pA-Gd 和 18A-Gd。37pA-Gd 和 18A-Gd 的直径分别为 7.6nm 和 8.0nm，纵向弛豫率分别为 9.8 和 10.0（mM s）（-1）。37pA 具有更好的脂质结合特性。在 J774A.1 巨噬细胞的体外试验中，证明这些颗粒通过引发胆固醇外流而具有 HDL 的功能，并且以类似于受体的方式被细胞摄取。两种试剂都使载脂蛋白 E 敲除小鼠的动脉粥样硬化斑块增强了约 90%（每个试剂 7 只），并且通过主动脉切片的共聚焦显微镜证明是巨噬细胞特异性的。37pA-Gd 和 18A-Gd 的半衰期分别为 2.6h 和 2.1h。尽管 37pA 具有更有利的脂质相互作用，但两种试剂在使用 MRI 检测动脉粥样硬化巨噬细胞方面都提供了类似的、优异的对比效果。
