Probing Myeloid Cell Dynamics in Ischaemic Heart Disease by Nanotracer Hot-Spot Imaging

Abstract

Ischemic heart disease evokes a complex immune response. However, tools to noninvasively track leukocytes’ systemic behaviour and dynamics 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 (MRI). The 19F-HDL nanotracer is additionally labelable with 89Zr and fluorophores to respectively detect myeloid cells by in vivo positron emission tomography (PET) imaging and optical modalities. 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-MRI. Concurrently, using ex vivo techniques, we were able to show that circulating pro-inflammatory myeloid cells accumulated in atherosclerotic plaques and 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.