Abstract
Pathological fibrosis of the liver is a landmark feature in chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Diagnosis and assessment of progress or treatment efficacy today requires biopsy of the liver, which is a challenge in, e.g., longitudinal interventional studies. Molecular imaging techniques such as positron emission tomography (PET) have the potential to enable minimally invasive assessment of liver fibrosis. This review will summarize and discuss the current status of the development of innovative imaging markers for processes relevant for fibrogenesis in liver, e.g., certain immune cells, activated fibroblasts, and collagen depositions.
Highlights
In normal physiology, fibrosis is an encapsulating and reparatory process in response to injury
Persistent inflammation in the liver may trigger the activation of stellate cells and fibroblasts, which in turn are responsible for the production and deposition of the extracellular matrix such as collagen, which is a hallmark of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) [4]
A positron emission tomography (PET) tracer was recently developed for the hepatocyte-specific asialoglycoprotein receptor (ASGPR), which is known to become decreased as NASH progresses [75]
Summary
Fibrosis is an encapsulating and reparatory process in response to injury. It is crucially important to develop noninvasive methods in order to detect, diagnose, stage, and study the molecular processes that drive the pathology of fibrosis. This would potentially contribute to an early-stage accurate staging of the disease and enable assessment of the effect of an intervention, such as lifestyle or drug treatment. Molecular imaging techniques in clinical, routine applications often involve contrast agents and include positron emission tomography (PET) and singlephoton emission tomography (SPECT), as well as certain MRI sequences. PET is of interest in the setting of imaging of molecular processes involved in fibrosis, as it is a highly sensitive, quantitative, and non-observer-dependent medical imaging technique using radiolabeled molecules for tracking biological processes and receptors. The focus will be on recent progress in PET radiopharmaceuticals, while contrasting these developments with established imaging markers
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