This project aims to overcome the diagnostic and therapeutic shortcomings of Systemic Sclerosis (SSc). Recently, there is a lack of sensitive, disease specific imaging tools allowing the detection of organ involvement at earliest, potentially still reversible diseases stages. In addition, there is a lack of clinically effective, specific anti-fibrotic therapies.
Therefore, in this project Nuclear PET and SPECT/CT will be validated in different representative animal models of SSc, including theBleomycin-induced skin fibrosis, TSK-1 and fra-2 tg mouse model. For nuclear imaging, radiotracers are used which are targeted against pathophysiologic key players of SSc, thereby visualizing the key pathophysiological pathways of SSc: microangiopathy, inflammation and fibrosis.These non-invasive in vivo nuclear imaging techniques are validated against the gold-standard ex vivo detection methods of vasculopathy, inflammation and fibrosis.Furthermore, as a noveltherapeutic approach,immunization of SSc mouse models against potential molecular key players, including IL-1 or IL-6, will be performed and therapeutic responses will be monitored in vivo using nuclear imaging.Once validated in SSc animal models, nuclear imaging techniques could be in a next step tested in humans to detect early organ involvement and to monitor disease processes as well as therapeutic responses.