Neutrophils play a complex role during onset of tissue injury as well as subsequent resolution and healing. To more precisely assess neutrophil dynamics upon cardiovascular injury, this study aimed at developing a noninvasive, background-free approach for specific mapping of murine and human neutrophils dynamics by whole-body MRI. For this, targeted multimodal fluorine-loaded nanotracers were engineered with binding peptides specifically directed against murine and human neutrophils, respectively. Intravenous tracer application for in vivo labelling of neutrophils prior to injury allowed the non-invasive 3D visualization of neutrophils within their different hematopoietic niches over the entire body and the subsequent monitoring of their egress into affected tissues. Stimulated murine/human neutrophils exhibited enhanced labelling due to upregulation of their target receptors which could be exploited as an in vivo readout for their activation state in both sterile and nonsterile cardiovascular inflammation. In summary, the present talk demonstrates that both human and murine neutrophils can be specifically targeted to track their dynamic trafficking by non-invasive MRI in vivo. In clinical translation, this approach will allow not only to identify hidden origins of bacterial or sterile inflammation in patients but also to unravel cardiovascular disease states that are on the verge of severe aggravation due to enhanced neutrophil infiltration or activation.

Acknowledgements

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References

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