FAP-catalyzed in situ self-assembly of magnetic resonance imaging probe for early and precise staging of liver fibrosis.

Abstract

Liver fibrosis is an inevitable stage in the progression of most chronic liver diseases. Early diagnosis and treatment of liver fibrosis are crucial for effectively managing chronic liver conditions. However, there lacks a noninvasive and sensitive imaging method capable of early assessing fibrosis activity. Here, we report a molecular magnetic resonance imaging (MRI) probe for imaging fibroblast activation protein (FAP), which is overexpressed on activated hepatic stellate cells (HSCs) even in very early fibrotic livers. This method relies on FAP-catalyzed in situ self-assembly of its substrate probe that leads to the increase of the rotational correlation time (τ_R) of probe, thereby notably amplifies T₁ MRI signal. Thanks to the superior specificity and efficiency of enzymatic reaction, our method has been validated as highly selective and sensitive to FAP in two liver fibrosis mouse models. By establishing a direct correlation between MRI signals and fibrosis activity, our method enables continuous monitoring of liver fibrotic disease progression and assessment of treatment responses.