Systemic Sclerosis; Radiotracer; Positron Emission Tomography (PET); Radiopharmacy; Vaccination therapy; Molecular Imaging
Schniering Janine, Maurer Britta, Distler Oliver (2019), Vascular Mechanisms in Systemic Sclerosis, Springer International Publishing, Cham, 27-37.
Schniering Janine, Benešová Martina, Brunner Matthias, Haller Stephanie, Cohrs Susan, Frauenfelder Thomas, Vrugt Bart, Feghali-Bostwick Carol A, Schibli Roger, Distler Oliver, Mueller Cristina, Maurer Britta (2019), Visualisation of interstitial lung disease by molecular imaging of integrin αvβ3 and somatostatin receptor 2, in Annals of the Rheumatic Diseases
, 78(2), 218-227.
Schniering Janine, Guo Li, Brunner Matthias, Schibli Roger, Ye Shuang, Distler Oliver, Béhé Martin, Maurer Britta (2018), Evaluation of 99mTc-rhAnnexin V-128 SPECT/CT as a diagnostic tool for early stages of interstitial lung disease associated with systemic sclerosis, in Arthritis Research & Therapy
, 20(1), 183-183.
Fettelschoss-Gabriel Antonia, Fettelschoss Victoria, Olomski Florian, Birkmann Katharina, Thoms Franziska, Bühler Maya, Kummer Martin, Zeltins Andris, Kündig Thomas M., Bachmann Martin F. (2018), Active vaccination against interleukin-5 as long-term treatment for insect-bite hypersensitivity in horses, in Allergy
Fettelschoss-Gabriel Antonia, Fettelschoss Victoria, Thoms Franziska, Giese Christoph, Daniel Michelle, Olomski Florian, Kamarachev Jivko, Birkmann Katharina, Bühler Maya, Kummer Martin, Zeltins Andris, Marti Eliane, Kündig Thomas M., Bachmann Martin F. (2018), Treating insect-bite hypersensitivity in horses with active vaccination against IL-5, in Journal of Allergy and Clinical Immunology
, 142(4), 1194-1205.e3.
Schniering Janine, Borgna Francesca, Siwowska Klaudia, Benešová Martina, Cohrs Susan, Hasler Roger, van der Meulen Nicholas P., Maurer Britta, Schibli Roger, Müller Cristina (2018), In Vivo Labeling of Plasma Proteins for Imaging of Enhanced Vascular Permeability in the Lungs, in Molecular Pharmaceutics
, 15(11), 4995-5004.
Bachmann Martin F., Zeltins Andris, Kalnins Gints, Balke Ina, Fischer Nina, Rostaher Ana, Tars Kaspars, Favrot Claude (2018), Vaccination against IL-31 for the treatment of atopic dermatitis in dogs, in Journal of Allergy and Clinical Immunology
, 142(1), 279-281.e1.
Boss Silvan D., Müller Cristina, Siwowska Klaudia, Büchel Josephine I., Schmid Raffaella M., Groehn Viola, Schibli Roger, Ametamey Simon M. (2018), Reduced 18 F-Folate Conjugates as a New Class of PET Tracers for Folate Receptor Imaging, in Bioconjugate Chemistry
, 29(4), 1119-1130.
Spalinger Marianne R., Manzini Roberto, Hering Larissa, Riggs Julianne B., Gottier Claudia, Lang Silvia, Atrott Kirstin, Fettelschoss Antonia, Olomski Florian, Kündig Thomas M., Fried Michael, McCole Declan F., Rogler Gerhard, Scharl Michael (2018), PTPN2 Regulates Inflammasome Activation and Controls Onset of Intestinal Inflammation and Colon Cancer, in Cell Reports
, 22(7), 1835-1848.
Arnoldini Simon, Moscaroli Alessandra, Chabria Mamta, Hilbert Manuel, Hertig Samuel, Schibli Roger, Béhé Martin, Vogel Viola (2017), Novel peptide probes to assess the tensional state of fibronectin fibers in cancer, in Nature Communications
, 8(1), 1793-1793.
Müller Cristina, Farkas Renáta, Borgna Francesca, Schmid Raffaella M., Benešová Martina, Schibli Roger (2017), Synthesis, Radiolabeling, and Characterization of Plasma Protein-Binding Ligands: Potential Tools for Modulation of the Pharmacokinetic Properties of (Radio)Pharmaceuticals, in Bioconjugate Chemistry
, 28(9), 2372-2383.
Rauber Simon, Luber Markus, Weber Stefanie, Maul Lisa, Soare Alina, Wohlfahrt Thomas, Lin Neng-Yu, Dietel Katharina, Bozec Aline, Herrmann Martin, Kaplan Mark H, Weigmann Benno, Zaiss Mario M, Fearon Ursula, Veale Douglas J, Cañete Juan D, Distler Oliver, Rivellese Felice, Pitzalis Costantino, Neurath Markus F, McKenzie Andrew N J, Wirtz Stefan, Schett Georg, Distler Jörg H W, et al. (2017), Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells, in Nature Medicine
Siwowska Klaudia, Haller Stephanie, Bortoli Francesca, Benešová Martina, Groehn Viola, Bernhardt Peter, Schibli Roger, Müller Cristina (2017), Preclinical Comparison of Albumin-Binding Radiofolates: Impact of Linker Entities on the in Vitro and in Vivo Properties, in Molecular Pharmaceutics
, 14(2), 523-532.
Systemic sclerosis (SSc) is a multisystem autoimmune disease, in which vasculopathy, inflammation, and fibrosis result in a complex pattern of skin- and organ-based complications. The 10 year survival rate is as poor as 60%. The equally high morbidity does not only substantially decrease quality of life, but also represents a major socioeconomic burden. In the recent past, significant progress has been made in the identification of potential molecular and cellular targets for anti-fibrotic therapies with the help of appropriate animal models of SSc covering different aspects and combinations of disease pathophysiology. However, there is a lack of sensitive, disease-specific imaging tools allowing the detection of organ involvement at earliest, still reversible stages, and there is also a lack of clinically effective, specific antifibrotic therapies. This interdisciplinary Sinergia project aims to overcome the diagnostic and therapeutic shortcomings in SSc by joining scientific excellence in nuclear imaging (partner A), translational SSc research (partner B), and molecular-targeted immunization (partner C). Nuclear PET&SPECT/CT will be validated in different animal models of SSc using both novel as well as existing radiotracers which visualize key pathways of the SSc pathophysiology, i.e. microangiopathy (integrins), inflammation (activated macrophages expressing folate receptor (FR)-ß), inflammation-dependent (cannabinoid receptors) fibrosis, and inflammation-independent (integrins, fibroblast activation protein (FAP)) fibrosis. This sensitive and highly specific diagnostic approach should allow the detection of early preclinical organ involvement and help to monitor therapies. As a novel therapeutic concept, we propose the immunization of SSc mouse models against potential molecular key players in the pathogenesis of SSc including IL-1, IL-6, IL-12/23 (p40), IL-13, IL-17, and VEGF to specifically and sustainably inhibit these targeted molecules. Our approach could serve as a template for many other (multisystem) autoimmune diseases. Therefore, an optimized dissemination of new research results to enhance the scientific impact will be a key aspect of this consortium. Furthermore, the wide array of techniques used in this interdisciplinary proposal ranging from nuclear imaging methodologies, animal experiments, cellular and molecular biology methods to vaccine generation will provide a unique training opportunity for young researchers. The implementation of a structured and detailed mentoring program is also novel in such an interdisciplinary program and could prove efficacy and applicability for career development and education/teaching in this setting. If this project is successful, our approach will be translated from “bench to bedside” in clinical studies with SSc patients in order to optimize and personalize treatment in the future. Molecular imaging and vaccination therapies could thus lead to paradigm shift in the clinical care of SSc patients.