Translational and Molecular Imaging Institute , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States.
Department of Radiology , Spaarne Gasthuis , 2035 RC Haarlem , The Netherlands.
Bioconjug Chem. 2020 Feb 19;31(2):360-368. doi: 10.1021/acs.bioconjchem.9b00256. Epub 2019 Jun 7.
Nanotherapy has recently emerged as an experimental treatment option for atherosclerosis. To fulfill its promise, robust noninvasive imaging approaches for subject selection and treatment evaluation are warranted. To that end, we present here a positron emission tomography (PET)-based method for quantification of liposomal nanoparticle uptake in the atherosclerotic vessel wall. We evaluated a modular procedure to label liposomal nanoparticles with the radioisotope zirconium-89 (Zr). Their biodistribution and vessel wall targeting in a rabbit atherosclerosis model was evaluated up to 15 days after intravenous injection by PET/computed tomography (CT) and PET/magnetic resonance imaging (PET/MRI). Vascular permeability was assessed using three-dimensional dynamic contrast-enhanced MRI (3D DCE-MRI) and using near-infrared fluorescence (NIRF) imaging. The Zr-radiolabeled liposomes displayed a biodistribution pattern typical of long-circulating nanoparticles. Importantly, they markedly accumulated in atherosclerotic lesions in the abdominal aorta, as evident on PET/MRI and confirmed by autoradiography, and this uptake moderately correlated with vascular permeability. The method presented herein facilitates the development of nanotherapy for atherosclerotic disease as it provides a tool to screen for nanoparticle targeting in individual subjects' plaques.
纳米疗法最近作为动脉粥样硬化的一种实验性治疗选择出现。为了实现其承诺，需要稳健的非侵入性成像方法来进行受试者选择和治疗评估。为此，我们在此提出了一种基于正电子发射断层扫描（PET）的方法，用于定量评估载脂蛋白体纳米颗粒在动脉粥样硬化血管壁中的摄取。我们评估了一种模块化程序，用放射性同位素锆-89（Zr）标记载脂蛋白体纳米颗粒。通过 PET/计算机断层扫描（CT）和 PET/磁共振成像（PET/MRI），在静脉注射后 15 天内评估了它们在兔动脉粥样硬化模型中的生物分布和血管壁靶向性。使用三维动态对比增强磁共振成像（3D DCE-MRI）和近红外荧光（NIRF）成像评估血管通透性。Zr 放射性标记的载脂蛋白体显示出典型的长循环纳米颗粒的生物分布模式。重要的是，它们在腹主动脉的动脉粥样硬化病变中明显积聚，在 PET/MRI 上可见，并通过放射自显影证实，这种摄取与血管通透性中度相关。本文提出的方法为动脉粥样硬化疾病的纳米疗法的发展提供了一种工具，可用于筛选个体斑块中纳米颗粒的靶向性。
