Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
Atherosclerosis. 2011 Feb;214(2):325-30. doi: 10.1016/j.atherosclerosis.2010.11.027. Epub 2010 Nov 27.
The selective in vivo localization of antibody derivatives in atherosclerotic plaques may open novel diagnostic and therapeutic applications. Here, we present a comparative in vivo localization analysis of eight radioiodinated human monoclonal antibodies in apolipoprotein E-deficient (ApoE(-/-)) mice.
Animals were fed with a cholesterol-rich diet, followed by harvesting of the aorta 24h after intravenous antibody injection and investigated by autoradiographic analysis. Localization of F8 antibody on atherosclerotic plaque structures was further studied in three-color fluorescence microscopy.
The study revealed that the F8 antibody, specific to the alternatively spliced EDA domain of fibronectin, exhibited the highest plaque-targeting potential among the antibodies analyzed in this study, with an ability to preferentially localize to all plaques within the aorta. Targeting results were confirmed by injection of fluorescein-labeled F8 antibody, followed by three-color fluorescence microscopy analysis.
These findings open novel biomolecular avenues for the in vivo imaging of atherosclerotic plaques and for pharmacodelivery applications, since F8 had previously been reported by our group to strongly stain atherosclerotic plaques in human carotid arteries.
抗体衍生物在动脉粥样硬化斑块中的选择性体内定位可能开辟新的诊断和治疗应用。在这里，我们对载脂蛋白 E 缺陷（ApoE（-/-））小鼠中的八种放射性碘标记的人单克隆抗体进行了比较体内定位分析。
动物喂食富含胆固醇的饮食，然后在静脉注射抗体后 24 小时收获主动脉，并通过放射自显影分析进行研究。在三色荧光显微镜下进一步研究了 F8 抗体在动脉粥样硬化斑块结构上的定位。
该研究表明，针对纤连蛋白的交替剪接 EDA 结构域的 F8 抗体在本研究分析的抗体中表现出最高的斑块靶向潜力，能够优先定位于主动脉内的所有斑块。通过注射荧光素标记的 F8 抗体并进行三色荧光显微镜分析证实了靶向结果。
这些发现为动脉粥样硬化斑块的体内成像和药物传递应用开辟了新的生物分子途径，因为我们的研究小组之前报道 F8 抗体可强烈染色人类颈动脉中的动脉粥样硬化斑块。
