Feng Li1, Huihui Yan2, Jiyao Wang3, Cong Li4, Jian Wu5, Shengdi Wu1, Shengxiang Rao6, Xihui Gao4, Qu Jin4. 1. Department of Gastroenterology, Fudan University-Affiliated Zhongshan Hospital, Shanghai, China. 2. Department of Gastroenterology, Fudan University-Affiliated Zhongshan Hospital, Shanghai, China; Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China. 3. Department of Gastroenterology, Fudan University-Affiliated Zhongshan Hospital, Shanghai, China; Shanghai Institute of Liver Diseases, Shanghai, China. Electronic address: wang.jiyao@zs-hospital.sh.cn. 4. Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai, China. 5. Shanghai Institute of Liver Diseases, Shanghai, China; Key Laboratory of Medical Molecular Virology, Ministries of Education and Public Health, Department of Medical Microbiology, Fudan University Shanghai Medical College, Shanghai, China. 6. Department of Radiology, Fudan University-Affiliated Zhongshan Hospital, Shanghai, China.
Abstract
AIMS: To explore the potential of a dendrimer nanoprobe labeled with cyclic arginine-glycine-aspartic acid pentapeptide (cRGDyK) as a magnetic resonance imaging (MRI) tracer to non-invasively differentiate the extent of liver fibrosis. METHODS: Synthetic dendrimer nanoprobes were labeled with cRGDyK (Den-RGD) to form a formulation of hepatic stellate cell (HSC)-specific MRI tracer. An MRI modality was employed to visualize hepatic Den-RGD deposition in a mouse model of liver fibrosis caused by thioacetamide treatment. RESULTS: Den-RGD bound to activated HSCs via integrin αvβ3 receptors. The labeling of nanoprobes with cRGDyK increased their affinity to and accelerated their uptake by activated HSCs. Most of intravenously administrated Den-RGD nanoprobes deposited in the fibrotic areas, and the deposited amount was paralleled with the severity of liver fibrosis. Majority of cells taking-up Den-RGD was found to be activated HSCs in fibrotic livers. An MRI modality using Den-RGD as a tracer demonstrated that the relative hepatic T1-weighed MR signal value was increased in parallel with the severity of liver fibrosis. CONCLUSION: The extent of Den-RGD deposition reflects integrin αvβ3 expression in activated HSCs, and Den-RGD appears to be a useful formulation of MRI tracer and may non-invasively and quantitatively assess the extent of liver fibrosis.
AIMS: To explore the potential of a dendrimer nanoprobe labeled with cyclic arginine-glycine-aspartic acid pentapeptide (cRGDyK) as a magnetic resonance imaging (MRI) tracer to non-invasively differentiate the extent of liver fibrosis. METHODS: Synthetic dendrimer nanoprobes were labeled with cRGDyK (Den-RGD) to form a formulation of hepatic stellate cell (HSC)-specific MRI tracer. An MRI modality was employed to visualize hepatic Den-RGD deposition in a mouse model of liver fibrosis caused by thioacetamide treatment. RESULTS:Den-RGD bound to activated HSCs via integrin αvβ3 receptors. The labeling of nanoprobes with cRGDyK increased their affinity to and accelerated their uptake by activated HSCs. Most of intravenously administrated Den-RGD nanoprobes deposited in the fibrotic areas, and the deposited amount was paralleled with the severity of liver fibrosis. Majority of cells taking-up Den-RGD was found to be activated HSCs in fibrotic livers. An MRI modality using Den-RGD as a tracer demonstrated that the relative hepatic T1-weighed MR signal value was increased in parallel with the severity of liver fibrosis. CONCLUSION: The extent of Den-RGD deposition reflects integrin αvβ3 expression in activated HSCs, and Den-RGD appears to be a useful formulation of MRI tracer and may non-invasively and quantitatively assess the extent of liver fibrosis.
Authors: Jeanne M Horowitz; Sudhakar K Venkatesh; Richard L Ehman; Kartik Jhaveri; Patrick Kamath; Michael A Ohliger; Anthony E Samir; Alvin C Silva; Bachir Taouli; Michael S Torbenson; Michael L Wells; Benjamin Yeh; Frank H Miller Journal: Abdom Radiol (NY) Date: 2017-08