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Probing myeloid cell dynamics in ischaemic heart disease by nanotracer hot-spot imaging.
Nature Nanotechnology ( IF 38.3 ) Pub Date : 2020-04-20 , DOI: 10.1038/s41565-020-0642-4
Max L Senders 1, 2 , Anu E Meerwaldt 1, 3 , Mandy M T van Leent 1, 2 , Brenda L Sanchez-Gaytan 1, 4 , Jan C van de Voort 1 , Yohana C Toner 1 , Alexander Maier 1 , Emma D Klein 1 , Nathaniel A T Sullivan 1 , Alexandros Marios Sofias 1, 5 , Hannah Groenen 1 , Christopher Faries 1 , Roderick S Oosterwijk 1 , Esther M van Leeuwen 1 , Francois Fay 1, 6 , Elena Chepurko 7 , Thomas Reiner 8 , Raphael Duivenvoorden 1, 9 , Lior Zangi 7 , Rick M Dijkhuizen 3 , Sjoerd Hak 5 , Filip K Swirski 10, 11 , Matthias Nahrendorf 10, 11 , Carlos Pérez-Medina 1, 12 , Abraham J P Teunissen 1 , Zahi A Fayad 1 , Claudia Calcagno 1 , Gustav J Strijkers 1, 13 , Willem J M Mulder 1, 2, 14, 15
Affiliation  

Ischaemic heart disease evokes a complex immune response. However, tools to track the systemic behaviour and dynamics of leukocytes non-invasively in vivo are lacking. Here, we present a multimodal hot-spot imaging approach using an innovative high-density lipoprotein-derived nanotracer with a perfluoro-crown ether payload (19F-HDL) to allow myeloid cell tracking by 19F magnetic resonance imaging. The 19F-HDL nanotracer can additionally be labelled with zirconium-89 and fluorophores to detect myeloid cells by in vivo positron emission tomography imaging and optical modalities, respectively. Using our nanotracer in atherosclerotic mice with myocardial infarction, we observed rapid myeloid cell egress from the spleen and bone marrow by in vivo 19F-HDL magnetic resonance imaging. Concurrently, using ex vivo techniques, we showed that circulating pro-inflammatory myeloid cells accumulated in atherosclerotic plaques and at the myocardial infarct site. Our multimodality imaging approach is a valuable addition to the immunology toolbox, enabling the study of complex myeloid cell behaviour dynamically.

中文翻译:

通过nanotracer热点成像探测缺血性心脏病中的髓样细胞动力学。

缺血性心脏病引起复杂的免疫反应。然而,缺乏用于在体内非侵入性地追踪白细胞的系统行为和动力学的工具。在这里,我们提出了一种多模态热点成像方法,该方法使用了创新的高密度脂蛋白衍生的纳米示踪剂和全氟冠醚有效负载(19F-HDL),以通过19F磁共振成像跟踪髓样细胞。19F-HDL纳米示踪剂可以另外用锆89和荧光团标记,以分别通过体内正电子发射断层扫描成像和光学模态检测髓样细胞。使用我们的nanotracer在患有心肌梗塞的动脉粥样硬化小鼠中,我们通过体内19F-HDL磁共振成像观察到了脾脏和骨髓中快速的髓样细胞流出。同时,使用离体技术,我们发现循环的促炎性骨髓细胞积聚在动脉粥样硬化斑块和心肌梗塞部位。我们的多模态成像方法是免疫学工具箱的宝贵补充,可动态研究复杂的髓样细胞行为。
更新日期:2020-04-24
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