[18F]-Alfatide PET imaging of integrin αvß3 for the non-invasive quantification of liver fibrosis.
J Hepatol
; 73(1): 161-169, 2020 07.
Article
en En
| MEDLINE
| ID: mdl-32145257
ABSTRACT
BACKGROUND & AIMS:
The vitronectin receptor integrin αvß3 drives fibrogenic activation of hepatic stellate cells (HSCs). Molecular imaging targeting the integrin αvß3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvß3 on activated HSCs (aHSCs) in the injured liver. In this study, we sought to compare differences in the uptake of [18F]-Alfatide between normal and injured liver to evaluate its utility for assessment of hepatic fibrogenesis.METHODS:
PET with [18F]-Alfatide, non-enhanced CT, histopathology, immunofluorescence staining, immunoblotting and gene analysis were performed to evaluate and quantify hepatic integrin αvß3 levels and liver fibrosis progression in mouse models of fibrosis (carbon tetrachloride [CCl4] and bile duct ligation [BDL]). The liver AUC divided by the blood AUC over 30 min was used as an integrin αvß3-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 αvß3, which is mainly expressed on aHSCs. Autoradiography and histopathology confirmed the PET imaging results. Further, the mRNA and protein level of integrin αvß3 and its signaling complex were higher in CCl4 and BDL models than controls. The results obtained from analyses on human fibrotic liver sections supported the animal findings.CONCLUSIONS:
Imaging hepatic integrin αvß3 with PET and [18F]-Alfatide offers a potential non-invasive method for monitoring the progression of liver fibrosis. LAYSUMMARY:
Integrin αvß3 expression on activated hepatic stellate cells (aHSCs) is associated with HSC proliferation during hepatic fibrogenesis. Herein, we show that a radioactive tracer, [18F]-Alfatide, binds to integrin αvß3 with high affinity and specificity. [18F]-Alfatide could thus be used as a non-invasive imaging biomarker to track hepatic fibrosis progression.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Péptidos Cíclicos
/
Integrina alfaVbeta3
/
Tomografía de Emisión de Positrones
/
Células Estrelladas Hepáticas
/
Cirrosis Hepática
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Hepatol
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos