Noninvasive assessment of liver fibrosis in mini pigs using an 18F–AlF-NOTA-RGD2 PET/CT molecular probe
Wenrui Liu,
Hongwei Xu,
Haili Zhang,
Maodi Xie,
Yundi Liu,
Li Wang,
Xiaoai Wu,
Yinrui Feng,
Kefei Chen
Affiliations
Wenrui Liu
Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan, 610041, China
Hongwei Xu
Department of Liver Surgery, Center of Liver Transplantation, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
Haili Zhang
Department of Liver Surgery, Center of Liver Transplantation, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
Maodi Xie
Laboratory of Mitochondria and Metabolis, Wmest China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
Yundi Liu
Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan, 610041, China
Li Wang
Jiangsu Xinrui Pharmaceutical Co., Ltd, Jiangsu, 226500, China
Xiaoai Wu
Department of Nuclear Medicine, Laboratory of Clinical Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China; Corresponding author. Department of Liver Surgery, Center of Liver Transplantation, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
Yinrui Feng
Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan, 610041, China; Corresponding author. Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan, 610041, China
Kefei Chen
Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan, 610041, China; Department of Liver Surgery, Center of Liver Transplantation, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China; Corresponding author. Department of Liver Surgery, Center of Liver Transplantation, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
To evaluate the efficacy of the 18F–AlF-NOTA-RGD2 positron emission tomography (PET)/computed tomography (CT) molecular probe for the noninvasive staging of liver fibrosis in mini pigs, a potential alternative to invasive diagnostic methods was revealed. This study used 18F–AlF-NOTA-RGD2 PET/CT imaging of mini pigs to assess liver fibrosis. The methods included synthesis and quality control of the molecular probe, establishment of an animal model of liver fibrosis, blood serum enzymatic tests, histopathological examination, PET/CT imaging, collagen content and expression, and mitochondrial reserve function assessment. The 18F–AlF-NOTA-RGD2 PET/CT molecular probe effectively differentiated various stages of liver fibrosis in mini pigs. Blood serum enzymatic tests revealed distinct stages of liver fibrosis, revealing significant increases in AST, ALT, TBIL, and DBIL levels as fibrosis advanced. Notably, ALT levels increased markedly in severe fibrosis patients. A gradual increase in collagen deposition and increasing α-SMA RNA expression and protein levels effectively differentiated between mild and severe fibrosis stages. Pathological examinations and Sirius Red staining confirmed these findings, highlighting substantial increases in collagen accumulation. PET/CT imaging results aligned with histopathological findings, showing that increased radiotracer uptake correlated with fibrosis severity. Assessments of mitochondrial function revealed a decrease in total liver glutathione content and mitochondrial reserve capacity, especially in patients with severe fibrosis. The 18F–AlF-NOTA-RGD2 PET/CT molecular probe is a promising tool for the noninvasive assessment of liver fibrosis, offering potential benefits over traditional diagnostic methods in hepatology.
