Evaluation of [18F]F-TZ3108 for PET Imaging of Metabolic-Associated Fatty Liver Disease

Peiyi Huang; Zhijun Li; Tukang Peng; Jihua Yang; Lei Bi; Guolong Huang; Yifan Qiu; Min Yang; Peizhen Ye; Mingxing Huang; Hongjun Jin; Liao Sun

doi:10.1007/s11307-022-01740-2

Evaluation of [¹⁸F]F-TZ3108 for PET Imaging of Metabolic-Associated Fatty Liver Disease

Mol Imaging Biol. 2022 Dec;24(6):909-919. doi: 10.1007/s11307-022-01740-2. Epub 2022 Jun 15.

Authors

Peiyi Huang^#^{1

2}, Zhijun Li^#², Tukang Peng², Jihua Yang¹, Lei Bi², Guolong Huang², Yifan Qiu², Min Yang², Peizhen Ye², Mingxing Huang³, Hongjun Jin⁴, Liao Sun⁵

Affiliations

¹ Department of Endocrinology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong Province, China.
² Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong Province, China.
³ Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong Province, China.
⁴ Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong Province, China. jinhj3@mail.sysu.edu.cn.
⁵ Department of Endocrinology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong Province, China. sunliao@mail.sysu.edu.cn.

^# Contributed equally.

PMID: 35705779
DOI: 10.1007/s11307-022-01740-2

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 (V_T), and the non-displacement binding potential (BP_ND) 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.

Keywords: ER-stress; MAFLD; Sig-1R; PET/CT; [18F]F-TZ3108.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Fluorodeoxyglucose F18*
Liver Diseases*
Mice
Positron Emission Tomography Computed Tomography / methods
Positron-Emission Tomography / methods
Tissue Distribution

Substances

Fluorodeoxyglucose F18