Phagocytosis of a PFOB-Nanoemulsion for 19F Magnetic Resonance Imaging: First Results in Monocytes of Patients with Stable Coronary Artery Disease and ST-Elevation Myocardial Infarction.

Fabian Nienhaus,Norbert Gerdes,Ulrich Flögel,Sebastian Temme,Vera Flocke,Florian Bönner,Annika Jahn,Malte Kelm,Susanne Pfeiler,Denise Colley

doi:10.3390/molecules24112058

Fabian Nienhaus, Norbert Gerdes + Show 8 more

Open Access

https://doi.org/10.3390/molecules24112058

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Abstract

Fluorine-19 magnetic resonance imaging (19F MRI) with intravenously applied perfluorooctyl bromide-nanoemulsions (PFOB-NE) has proven its feasibility to visualize inflammatory processes in experimental disease models. This approach is based on the properties of monocytes/macrophages to ingest PFOB-NE particles enabling specific cell tracking in vivo. However, information on safety (cellular function and viability), mechanism of ingestion and impact of specific disease environment on PFOB-NE uptake is lacking. This information is, however, crucial for the interpretation of 19F MRI signals and a possible translation to clinical application. To address these issues, whole blood samples were collected from patients with acute ST-elevation myocardial infarction (STEMI), stable coronary artery disease (SCAD) and healthy volunteers. Samples were exposed to fluorescently-labeled PFOB-NE and particle uptake, cell viability and migration activity was evaluated by flow cytometry and MRI. We were able to show that PFOB-NE is ingested by human monocytes in a time- and subset-dependent manner via active phagocytosis. Monocyte function (migration, phagocytosis) and viability was maintained after PFOB-NE uptake. Monocytes of STEMI and SCAD patients did not differ in their maximal PFOB-NE uptake compared to healthy controls. In sum, our study provides further evidence for a safe translation of PFOB-NE for imaging purposes in humans.

Highlights

Non-invasive visualization of macrophages is of paramount interest in various clinical inflammatory diseases, since those cells impact on prognosis
No significant differences in perfluorooctyl bromide-nanoemulsions (PFOB-NE) uptake of human monocytes could be observed
No significant differences in PFOB-NE uptake of human monocytes could be observed between patients with ST-elevation myocardial infarction (STEMI), stable coronary artery disease (SCAD) and healthy volunteers

Summary

Introduction

Non-invasive visualization of macrophages is of paramount interest in various clinical inflammatory diseases, since those cells impact on prognosis. Has proven its feasibility to visualize inflammatory processes in a wide range of experimental disease models (e.g., myocardial infarction, stroke, graft rejection, myocarditis) [3,4,5,6,7,8]. This imaging approach is based on the properties of monocytes/macrophages to ingest PFC-NE particles with high affinity, which allows a cell type-specific tracking in vivo [3].

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