Collagen Targeted Contrast Agents

Repeated hepatic injury – due to alcohol excess, hepatitis B or C infection, diabetes, fatty liver disease or metabolic syndrome – induces activation of tissue repair mechanisms to replace necrotic tissue with extracellular matrix scar tissue, thereby leading to liver fibrosis. If left unchecked, advanced fibrosis leads to impaired liver function and the development of hepatocellular carcinoma (HCC), both of which increase the risk of death. Currently, the gold standard for assessing liver fibrosis is tissue biopsy. However liver biopsy is invasive, has sampling errors, and is not optimal for screening, monitoring, or clinical decision-making. Of note, even for advanced stages of liver fibrosis, such as cirrhosis, error rates in diagnosis of 33% have been reported. Therefore, there is a critical need for non-invasive techniques that can repeatedly assess liver fibrosis throughout the whole organ, identify disease progression, and asses response to potential therapeutic agents.

Fibrosis is characterized by excessive accumulation of extracellular matrix proteins including type I collagen. We have previously identified a 16 amino acid peptide that had specificity for type 1 collagen and functionalized it for MRI through the addition of three Gd-DTPA chelators. The collagen targeted probe, termed EP-3533, was used previously to image liver fibrosis in two rodent models (diethylnitrosamine-treated rats and carbon tetrachloride-treated mice) of late-stage liver fibrosis. We are now investigating the ability of EP-3533 to longitudinally monitor the progression of liver fibrosis as well as to asses the efficacy of different therapeutic agents.