Molecular imaging and biology · 2018
A Non-Peptidic S100A9 Specific Ligand for Optical Imaging of Phagocyte Activity In Vivo.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Völler Tom, Faust Andreas, Roth Johannes, Schäfers Michael, Vogl Thomas, Hermann Sven
Аннотация
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.
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.