LIVERFIBROSISIMAGING

Quantitative Imaging of Liver Fibrosis and Fibrogenesis

Coordinatore	UNIVERSITATSMEDIZIN DER JOHANNES GUTENBERG-UNIVERSITAT MAINZ    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Germany [DE]
Totale costo	2˙454˙603 €
EC contributo	2˙454˙603 €
Programma	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)
Code Call	ERC-2011-ADG_20110310
Funding Scheme	ERC-AG
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-08-01   -   2017-07-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	JOHANNES GUTENBERG UNIVERSITAET MAINZ  Organization address address: SAARSTRASSE 21 city: MAINZ postcode: 55099 contact info Titolo: Ms. Nome: Julia Cognome: Doré Email: send email Telefono: +49 6131 3926865 Fax: +49 6131 3924741	DE (MAINZ)	beneficiary	629˙109.20
2	MEDIZINISCHE HOCHSCHULE HANNOVER  Organization address address: Carl-Neuberg-Strasse 1 city: HANNOVER postcode: 30625 contact info Titolo: Mr. Nome: Frank Cognome: Dittrich Email: send email Telefono: 495115000000	DE (HANNOVER)	beneficiary	246˙384.40
3	UNIVERSITATSMEDIZIN DER JOHANNES GUTENBERG-UNIVERSITAT MAINZ  Organization address address: Langenbeckstrasse 1 city: Mainz postcode: 55131 contact info Titolo: Dr. Nome: Silvia Cognome: Tschauder Email: send email Telefono: +49 6131 179695 Fax: +49 6131 179669	DE (Mainz)	hostInstitution	1˙579˙110.00
4	UNIVERSITATSMEDIZIN DER JOHANNES GUTENBERG-UNIVERSITAT MAINZ  Organization address address: Langenbeckstrasse 1 city: Mainz postcode: 55131 contact info Titolo: Prof. Nome: Detlef Cognome: Schuppan Email: send email Telefono: +49 6131 177356 Fax: +49 6131 177357	DE (Mainz)	hostInstitution	1˙579˙110.00

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 Obiettivo del progetto (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.'