Tom Völler1,2, Andreas Faust3,4, Johannes Roth1,4,5, Michael Schäfers3,4,6, Thomas Vogl1,4,5, Sven Hermann7,8. 1. Institute of Immunology, University Hospital Münster, Röntgenstr. 21, 48149, Münster, Germany. 2. Institute of Microbiology, ETH Zurich, Vladimir-Prelog Weg 4, 8093, Zurich, Switzerland. 3. European Institute for Molecular Imaging (EIMI), University of Münster, Waldeyerstr. 15, 48149, Münster, Germany. 4. Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), University of Münster, 48149, Münster, Germany. 5. Interdisciplinary Center for Clinical Research (IZKF Münster), University of Münster, Domagkstr. 3, 48149, Münster, Germany. 6. Department of Nuclear Medicine, University Hospital of Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany. 7. European Institute for Molecular Imaging (EIMI), University of Münster, Waldeyerstr. 15, 48149, Münster, Germany. shermann@uni-muenster.de. 8. Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), University of Münster, 48149, Münster, Germany. shermann@uni-muenster.de.
Abstract
PURPOSE: Non-invasive assessment of inflammatory activity in the course of various diseases is a largely unmet clinical challenge. An early feature of inflammation is local secretion of the alarmin S100A8/A9 by activated phagocytes. We here evaluate a novel S100A9-targeted small molecule tracer Cy5.5-CES271 for in vivo optical imaging of inflammatory activity in exemplary disease models. PROCEDURES: Dynamics of Cy5.5-CES271 was characterized in a model of irritant contact dermatitis by sequential fluorescence reflectance imaging (FRI) up to 24 h postinjection (p.i.). Specificity of Cy5.5-CES271 binding to S100A9 in vivo was examined by blocking studies and by employing S100A9-/- mice. Finally, S100A9 secretion in acute lung inflammation was assessed by Cy5.5-CES271 and FRI of explanted lungs. RESULTS: In ear inflammation, we were able to non-invasively follow the time course of S100A9 expression using Cy5.5-CES271 and FRI over 24 h p.i. (peak activity at 3 h p.i.). Specificity of imaging could be shown by a significant signal reduction after predosing and using S100A9-/- mice. In acute lung injury, local and systemic S100A8/A9 levels increased over time and correlated significantly with FRI signal levels in explanted lungs. CONCLUSIONS: Cy5.5-CES271 shows significant accumulation in models of inflammatory diseases and specific binding to S100A9 in vivo. This study, for the first time, demonstrates the potential of a small molecule non-peptidic tracer enabling imaging of S100A9 as a marker of local phagocyte activity in inflammatory scenarios suggesting this compound class for translational attempts.
PURPOSE: Non-invasive assessment of inflammatory activity in the course of various diseases is a largely unmet clinical challenge. An early feature of inflammation is local secretion of the alarmin S100A8/A9 by activated phagocytes. We here evaluate a novel S100A9-targeted small molecule tracer Cy5.5-CES271 for in vivo optical imaging of inflammatory activity in exemplary disease models. PROCEDURES: Dynamics of Cy5.5-CES271 was characterized in a model of irritant contact dermatitis by sequential fluorescence reflectance imaging (FRI) up to 24 h postinjection (p.i.). Specificity of Cy5.5-CES271 binding to S100A9 in vivo was examined by blocking studies and by employing S100A9-/- mice. Finally, S100A9 secretion in acute lung inflammation was assessed by Cy5.5-CES271 and FRI of explanted lungs. RESULTS: In ear inflammation, we were able to non-invasively follow the time course of S100A9 expression using Cy5.5-CES271 and FRI over 24 h p.i. (peak activity at 3 h p.i.). Specificity of imaging could be shown by a significant signal reduction after predosing and using S100A9-/- mice. In acute lung injury, local and systemic S100A8/A9 levels increased over time and correlated significantly with FRI signal levels in explanted lungs. CONCLUSIONS:Cy5.5-CES271 shows significant accumulation in models of inflammatory diseases and specific binding to S100A9 in vivo. This study, for the first time, demonstrates the potential of a small molecule non-peptidic tracer enabling imaging of S100A9 as a marker of local phagocyte activity in inflammatory scenarios suggesting this compound class for translational attempts.
Authors: G Comi; A Pulizzi; M Rovaris; O Abramsky; T Arbizu; A Boiko; R Gold; E Havrdova; S Komoly; Kw Selmaj; B Sharrack; M Filippi Journal: Lancet Date: 2008-06-21 Impact factor: 79.321
Authors: Ahmed Achouiti; Thomas Vogl; Constantin F Urban; Marc Röhm; Tijmen J Hommes; Marieke A D van Zoelen; Sandrine Florquin; Johannes Roth; Cornelis van 't Veer; Alex F de Vos; Tom van der Poll Journal: PLoS Pathog Date: 2012-10-25 Impact factor: 6.823