OP0155 New Optical in Vivo Imaging of the Alarmin S100A9 in an Experimental Autoimmune Model of Rheumatoid Arthritis
Authors: S. Zenker, M. Kondapuram, J. Roth, S. Hermann, A. Faust, M. Schäfers, T. Vogl
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Members of the alarmin family are key molecules to promote and exacerbate inflammatory responses such as arthritis. Elevated levels of S100A8/S100A9 (MRP8/14) in serum and synovial fluids correlate very well with disease activity in rheumatoid and psoriatric arthritis<sup>1</sup>. We recently demonstrated that S100A9 is a good biomarker to monitor local inflammatory activities in various inflammatory diseases using <i>in vivo</i> imaging based on labeled antibodie<sup>2</sup>. <h3>Objectives</h3> In our present optical imaging study we used a small molecular compound as specific probe for targeting S100A9 in the acute phase of Collagen-Induced Arthritis (CIA) mouse model. We used a fluorescently-labeled compound (CES-271) which has been described earlier to bind specifically to S100A9<sup>3</sup>. <h3>Methods</h3> DBA/1J mice were immunized with bovine type II collagen or PBS emulsified in Complete Freund9s Adjuvant. On day 21, mice received a booster injection of collagen dissolved in PBS or only PBS. Mice were scored at least 3 times/ week for the visual appearance of arthritis in the peripheral joints using an 3-point score: 0=normal; 1=mild but definitely visible, erythema and oedema of one digit/toe or limb; 2=erythema and moderate oedema of at least two digits/toe or limb; 3=erythema, severe oedema of the entire paw and/or rigidity. The optical <i>in vivo</i> imaging was done after arthritis was clinically detectable after application of CES271-Cy5.5 by FRI (Bruker In-Vivo FXPro). ProSense750 (Perkin Elmer) was injected as internal control of inflammation. At the end of the experiment, serum was analyzed for S100A8/S100A9 by ELISA and paws were processed for histology. <h3>Results</h3> CIA-mice developed clear signs of arthritis in comparison to control mice witch correlates well with optical data and bright field images. In comparison to the non-specific ProSense750 S100A9 ligand CES271-Cy5.5 showed an excellent signal to noise ratio. Furthermore serum and histology data showed a similar pattern of S100A9 expression compared to imaging data. <h3>Conclusions</h3> Our <i>in vivo</i> optical imaging study suggest that the novel S100A9-ligand CES271 has as great potential for visualizing the inflammatory activities of arthritis <i>in vivo</i>. Due to the correlation with the S100A9 expression, the new tracer CES271 could provide as new fluorescence imaging method for local diagnosis of inflammatory activity in rheumatoid arthritis patients. <h3>References</h3> Chan, J, Roth, J, Oppenheim, J, Tracey, K, Vogl, T., Feldmann, M, Horwood, N, &amp; Nanchahal, J. (2012) Alarmins: Awaiting a Clinical Response, J. Clin. Invest. 122, 2711-2719 Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity; Thomas Vogl, Michel Eisenblätter, Tom Völler, Stefanie Zenker, Sven Hermann, Peter van Lent, Andreas Faust, Christiane Geyer, Beatrix Petersen, Kirsten Roebrock, Michael Schäfers, Christoph Bremer &amp; Johannes Roth; Nature communications; 2014; 5:4593; DO: 10: 1038 Björk, P., Björk, A., Vogl, T., Stenström, M., Liberg, D., Olsson, A., Roth, J., Ivars, F. &amp; Leanderson, T. (2009) Identification of human S100A9 as a novel target for treatment of autoimmune disease via their binding to quinoline-3-carboxamides, PLoS Biol. 7, e97d <h3>Disclosure of Interest</h3> None declared