Objective Chronic liver disease can progress to cirrhosis, with death due to liver failure and cancer. Cirrhosis prevalence in the EU is 0.5%-1%. However, development of therapies that prevent progression to cirrhosis is hampered by the lack of a sensitive, non-invasive method to quantify fibrosis or fibrosis progression (fibrogenesis). Liver biopsy 1) is risky, 2) shows high sampling variability, and 3) is too insensitive to assess fibrosis progression in clinical studies. Conventional radiological imaging, serum markers, and ultrasound- or MR-elastography do neither permit exact fibrosis nor any fibrogenesis measurement.We plan to develop a clinically applicable methodology to quantitate fibrosis and fibrogenesis over the whole liver using imaging agents that target and thus quantify abundant fibrillar collagen or key cells that drive fibrogenesis (activated myofibroblasts and cholangiocytes). We demonstrated the feasibility of this approach using radiolabeled conjugates of high affinity that target integrin alphaVbeta6 and PDGFbeta receptor that are cell surface molecules of activated cholangiocytes and myofibroblasts. i.v. injection of the integrin conjugate allowed quantitative imaging of alphaVbeta6 expression and correlated with whole liver fibrogenesis. We intend to optimize nonpeptide and peptide ligands for integrin alphaVbeta6, PDGF beta receptor and fibrillar collagens using novel linkers and oligomerization, using PET-radioimaging with Ga-68, Sc-44 and F-18. The targeted imaging constructs will be validated in vivo using established rodent models with defined liver fibrosis and fibrogenesis, with and without antifibrotic drug therapy. Translation to phase I and II clinical studies is planned in years 4-5 of the project.The technology will for the first time allow for 1. individual risk assessment of fibrosis progression, and 2. rapid testing of antifibrotic drugs and their combinations in small groups of individual patients. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesmedical and health sciencesclinical medicineoncologymedical and health sciencesclinical medicinehepatologynatural sciencesphysical sciencesacousticsultrasound Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS7 - ERC Advanced Grant - Diagnostic tools, therapies and public health Call for proposal ERC-2011-ADG_20110310 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution UNIVERSITAETSMEDIZIN DER JOHANNES GUTENBERG-UNIVERSITAET MAINZ EU contribution € 1 579 110,00 Address Langenbeckstrasse 1 55131 Mainz Germany See on map Region Rheinland-Pfalz Rheinhessen-Pfalz Mainz, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Administrative Contact Silvia Tschauder (Dr.) Principal investigator Detlef Schuppan (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (3) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITAETSMEDIZIN DER JOHANNES GUTENBERG-UNIVERSITAET MAINZ Germany EU contribution € 1 579 110,00 Address Langenbeckstrasse 1 55131 Mainz See on map Region Rheinland-Pfalz Rheinhessen-Pfalz Mainz, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Administrative Contact Silvia Tschauder (Dr.) Principal investigator Detlef Schuppan (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data JOHANNES GUTENBERG-UNIVERSITAT MAINZ Germany EU contribution € 629 109,20 Address SAARSTRASSE 21 55122 Mainz See on map Region Rheinland-Pfalz Rheinhessen-Pfalz Mainz, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Administrative Contact Julia Doré (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data MEDIZINISCHE HOCHSCHULE HANNOVER Germany EU contribution € 246 384,40 Address Carl-Neuberg-Strasse 1 30625 Hannover See on map Region Niedersachsen Hannover Region Hannover Activity type Higher or Secondary Education Establishments Administrative Contact Frank Dittrich (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data