Polyglucose nanoparticles with renal elimination and macrophage avidity facilitate PET imaging in ischaemic heart disease.
Polyglucose nanoparticles with renal elimination and macrophage avidity facilitate PET imaging in ischaemic heart disease.
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DOI：
10.1038/ncomms14064
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发表时间：
2017-01-16
影响因子：
16.6
通讯作者：
Nahrendorf M
中科院分区：
文献类型：
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作者：
Keliher EJ;Ye YX;Wojtkiewicz GR;Aguirre AD;Tricot B;Senders ML;Groenen H;Fay F;Perez-Medina C;Calcagno C;Carlucci G;Reiner T;Sun Y;Courties G;Iwamoto Y;Kim HY;Wang C;Chen JW;Swirski FK;Wey HY;Hooker J;Fayad ZA;Mulder WJ;Weissleder R;Nahrendorf M
组织巨噬细胞数量在健康和疾病期间变化。大量的炎性巨噬细胞破坏组织，导致动脉粥样硬化、心肌梗死和心力衰竭。新出现的治疗方案引起了人们对监测患者巨噬细胞的兴趣。在这里，我们描述了18F-Macroflor的正电子发射断层扫描（PET）成像，这是一种对巨噬细胞具有高亲和力的改性聚葡萄糖纳米颗粒。由于其体积小，Macroflor是肾脏排泄的，这是同位素氟-18成像的先决条件。在包括灵长类动物在内的三种物种中，巨噬细胞的血液半衰期很短，这使得巨噬细胞能够在发炎的心血管组织中成像。Macroflor在心脏和斑块巨噬细胞中富集，从而增加小鼠梗死区以及小鼠和家兔动脉粥样硬化斑块的PET信号。在PET/磁共振成像（MRI）实验中，Macroflor PET成像检测巨噬细胞群体大小的变化，而分子MRI报告炎症的增加或消退。这些数据表明，Macroflor PET/MRI可以作为一种无创监测巨噬细胞生物学的临床工具。炎症的体内成像对于许多病理的检测和监测至关重要，无创巨噬细胞定量被认为是一种可能的方法。在这里，Keliher等人描述了一种新的聚糖纳米颗粒示踪剂，它可以通过肾脏快速排泄，并且对动脉粥样硬化斑块中的巨噬细胞具有高亲和力。
Tissue macrophage numbers vary during health versus disease. Abundant inflammatory macrophages destruct tissues, leading to atherosclerosis, myocardial infarction and heart failure. Emerging therapeutic options create interest in monitoring macrophages in patients. Here we describe positron emission tomography (PET) imaging with 18F-Macroflor, a modified polyglucose nanoparticle with high avidity for macrophages. Due to its small size, Macroflor is excreted renally, a prerequisite for imaging with the isotope flourine-18. The particle's short blood half-life, measured in three species, including a primate, enables macrophage imaging in inflamed cardiovascular tissues. Macroflor enriches in cardiac and plaque macrophages, thereby increasing PET signal in murine infarcts and both mouse and rabbit atherosclerotic plaques. In PET/magnetic resonance imaging (MRI) experiments, Macroflor PET imaging detects changes in macrophage population size while molecular MRI reports on increasing or resolving inflammation. These data suggest that Macroflor PET/MRI could be a clinical tool to non-invasively monitor macrophage biology. In vivo imaging of inflammation is crucial for detection and monitoring of many pathologies and noninvasive macrophage quantification has been suggested as a possible approach. Here Keliher et al. describe novel polyglucose nanoparticle tracers that are rapidly excreted by the kidney and with high affinity for macrophages in atherosclerotic plaques.