Liver fibrosis is a progressive and fatal disease characterized by the accumulation of excessive amounts of scar tissue in response to chronic liver injury. The disease proceeds asymptomatically, until clinical signs of liver failure occur only in a very late stage of the disease. Early diagnosis would offer better treatment options. However, early detection and quantification of fibrosis, as well as determining the rate of fibrosis progression (fibrogenesis) or reversal (fibrolysis) still depends on rudimentary and inaccurate methods. This proposal focuses on the development of a new method for the quantification of liver fibrosis and its dynamics, based on the design of molecular probes that can selectively pinpoint these processes in non-invasive imaging studies. To this end, novel disease markers of fibrosis, fibrogenesis and fibrolysis will be identified using state-of-the-art proteomic techniques, simultaneously taking into account that these markers will have to be easily accessible for intravenously-injected ligands in vivo. Based on the identified markers, binding probes will be synthesized and evaluated for their detection capabilities in fibrosis models. To this end, whole body imaging studies are used, combined with novel pharmacokinetic-modeling approaches, in which body distribution, cellular uptake and excretion of the new probes are correlated to disease parameters.
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