Probing myeloid cell dynamics in ischaemic heart disease by nanotracer hot-spot imaging

Max L. Senders, Anu E. Meerwaldt, Mandy M.T. van Leent, Brenda L. Sanchez-Gaytan, Jan C. van de Voort, Yohana C. Toner, Alexander Maier, Emma D. Klein, Nathaniel A.T. Sullivan, Alexandros Marios Sofias, Hannah Groenen, Christopher Faries, Roderick S. Oosterwijk, Esther M. van Leeuwen, Francois Fay, Elena Chepurko, Thomas Reiner, Raphael Duivenvoorden, Lior Zangi, Rick M. DijkhuizenSjoerd Hak, Filip K. Swirski, Matthias Nahrendorf, Carlos Pérez-Medina, Abraham J.P. Teunissen, Zahi A. Fayad, Claudia Calcagno, Gustav J. Strijkers, Willem J.M. Mulder

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)398-405
Number of pages8
JournalNature Nanotechnology
Volume15
Issue number5
DOIs
StatePublished - 1 May 2020

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