Collagen-targeted molecular imaging in diffuse liver diseases
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SPECIAL SECTION: CHRONIC LIVER DISEASE
Collagen‑targeted molecular imaging in diffuse liver diseases Iris Y. Zhou1,2,3 · Kenneth K. Tanabe4 · Bryan C. Fuchs5 · Peter Caravan1,2,3 Received: 12 April 2020 / Revised: 10 July 2020 / Accepted: 18 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Liver fibrosis is a common pathway shared by all progressive chronic liver diseases (CLD) regardless of the underlying etiologies. With liver biopsy being the gold standard in assessing fibrosis degree, there is a large unmet clinical need to develop non-invasive imaging tools that can directly and repeatedly quantify fibrosis throughout the liver for a more accurate assessment of disease burden, progression, and treatment response. Type I collagen is a particularly attractive target for molecular imaging as its excessive deposition is specific to fibrosis, and it is present in concentrations suitable for many imaging modalities. Novel molecular MRI contrast agents designed to bind with collagen provide direct quantification of collagen deposition, which have been validated across animal species and liver injury models. Collagen-targeted molecular imaging probes hold great promise not only as a tool for initial staging and surveillance of fibrosis progression, but also as a marker of fibrosis regression in drug trials. Keywords Molecular imaging · Collagen · ECM · Fibrosis · MRI
Introduction Chronic liver disease (CLD) is a common and serious public health burden. The major causes of CLD include non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), hepatic viral infections, alcohol abuse, chronic alteration of metabolism, or persistent autoimmune reaction [1]. NAFLD and NASH are the leading forms of CLD, and their worldwide prevalence continues to grow due to increasing incidence of diabetes and obesity in the USA and other regions [2, 3]. Liver fibrosis is a hallmark shared by almost all causes of progressive CLD. Without removal of exposure to the specific etiology, fibrosis tends to progress, leading * Peter Caravan [email protected] 1
Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA
2
Harvard Medical School, 149 13th St, Boston, MA 02129, USA
3
Institute for Innovation in Imaging (i3), Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
4
Division of Surgical Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
5
Ferring Research Institute, San Diego, CA, USA
to hepatic dysfunction, portal hypertension, and ultimately culminating in liver cirrhosis. Moreover, the presence and severity of fibrosis are the main prognostic factors for clinical outcomes in patients with CLD. Therefore, it is crucial to be able to differentiate liver fibrosis stages since treatment decision and monitoring algorithms are related to the degree of fibrosis [4–6]. Liver biopsy is still considered the gold standard for detecting and staging liver fibrosis; however, biops
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