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.
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The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.
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This work was supported by De Drie Lichten Foundation in the Netherlands (M.L.S.); American Heart Association grant nos. 17PRE33660729 (M.L.S.) and 16SDG3139000 (C.P.M.); German Research Foundation grant nos. MA 7059/1 (A.M.) and HO 5953/1-1 (M.N.); National Heart, Lung, and Blood Institute grant nos. HL096576, HL117829, HL139598 and HL128264; the MGH Research Scholar Award (M.N. and F.K.S.); Dutch Applied and Engineering Sciences (TTW) grant no. 14716 (G.J.S); National Institutes of Health (NIH) grants: R01HL143814, R01HL144072, R01HL135878 and P01HL131478 (Z.A.F.); R01HL144072, R01CA220234 and P01HL131478 (W.J.M.M.); and the Netherlands Organisation for Scientific Research (NWO) grants: Vidi 91713324 and Vici 91818622 (W.J.M.M.).
The authors declare no competing interests.
Peer review information Nature Nanotechnology thanks Jeff Bulte, Christian Schulz and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Senders, M.L., Meerwaldt, A.E., van Leent, M.M.T. et al. Probing myeloid cell dynamics in ischaemic heart disease by nanotracer hot-spot imaging. Nat. Nanotechnol. 15, 398–405 (2020). https://doi.org/10.1038/s41565-020-0642-4
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