[18F]- Alfatide PET imaging of integrin αvβ3 for the non-invasive quantification of liver fibrosis

Abstract Background & Aims The vitronectin receptor integrin alpha v beta 3 (αvβ3) drives fibrogenic activation of hepatic stellate cells (HSC). Molecular imaging targeting the integrin αvβ3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvβ3 on activated HSCs (aHSCs) in the injured liver. In this study, we sought to compare differences in uptake of the [18F]-Alfatide between normal and injured liver to evaluate its utility for assessment of hepatic fibrogenesis. Methods PET with [18F]-Alfatide, non-enhanced computerized tomography (CT), histopathology, immunofluorescence staining, immunoblotting and gene analysis were performed to evaluate and quantify hepatic integrin αvβ3 levels and liver fibrosis progression in carbon-tetrachloride (CCl4) and bile duct ligation (BDL) induced liver fibrosis mice model. The AUC liver 0–30 min to AUC blood 0–30 min contrast was used as an integrin αvβ3–PET index to quantify fibrosis progression. Ex vivo analysis of frozen liver tissue from patients with fibrosis and cirrhosis verified the animal findings. Results Fibrotic mouse livers showed enhanced [18F]-Alfatide uptake and retention compared to control livers. The radiotracer was demonstrated to bind specifically with integrin αvβ3 mainly expressed on aHSCs. Autoradiography and histopathology confirmed the PET imaging results. Further, the mRNA and protein level of integrin αvβ3 and its signaling complex were higher in CCl4 and BDL models compared to controls. Human fibrotic liver section results supported the animal findings. Conclusions Imaging hepatic integrin αvβ3 with PET and [18F]-Alfatide offers a potential noninvasive method for monitoring the progression of liver fibrosis.