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Evaluation of [18F]F-TZ3108 for PET Imaging of Metabolic-Associated Fatty Liver Disease.
- Source :
-
Molecular Imaging & Biology . Dec2022, Vol. 24 Issue 6, p909-919. 11p. - Publication Year :
- 2022
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Abstract
- Purpose: Sigma-1 receptor (Sig-1R), a chaperone that resides at the mitochondrion-associated endoplasmic reticulum (ER) membrane, is an ER stress biomarker. It is thought that ER stress plays a critical role in the progression of metabolic-associated fatty liver disease (MAFLD). The aim of this study was to evaluate a positron emission tomography (PET) tracer [18F]F-TZ3108 targeting Sig-1R for MAFLD. Procedures: The mouse model of MAFLD was established by feeding high-fat diet (HFD) for 12 weeks. Dynamic (0–60 min) PET/CT scans were performed after intravenous injection of 2-deoxy-2[18F]fluoro-D-glucose ([18F]-FDG) and [18F]F-TZ3108. Tracer kinetic modeling was performed for quantification of the PET/CT imaging of the liver. Post-PET biodistribution, the liver tissue western blotting (WB), and immunofluorescence (IF) were performed to compare the expression of Sig-1R levels in the organs harvested from both MAFLD and age-matched control mice. Results: The micro PET/CT imaging revealed a significantly decreased uptake of [18F]F-TZ3108 in the livers of the MAFLD group compared to the healthy controls, while the uptake of [18F]-FDG in the livers was not significantly different between the two groups. Based on the tracer kinetic modeling, the binding disassociate rate (k4) for [18F]F-TZ3108 was significantly increased in MAFLD group compared to healthy controls. The volume distribution (VT), and the non-displacement binding potential (BPND) revealed significantly decrease in MAFLD compared to healthy controls respectively. The post-PET biodistribution (%ID/g) of [18F]F-TZ3108 in the livers of MAFLD mice was significantly reduced nearly twofold than that in the livers of control mice. WB and IF experiments further confirmed the reduction of Sig-1R expression in the MAFLD group. Conclusions: The expression of Sig-1R in the liver, measured by the PET tracer, [18F]F-TZ3108, was significantly decreased in mouse model of MAFLD. The [18F]F-TZ3108 PET/CT imaging may provide a novel means of visualization for ER stress in MAFLD or other diseases in vivo. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15361632
- Volume :
- 24
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Molecular Imaging & Biology
- Publication Type :
- Academic Journal
- Accession number :
- 160349660
- Full Text :
- https://doi.org/10.1007/s11307-022-01740-2