Liu Wenrui, Xu Hongwei, Zhang Haili, Xie Maodi, Liu Yundi, Wang Li, Wu Xiaoai, Feng Yinrui, Chen Kefei
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.
Heliyon. 2024 Jul 31;10(15):e35502. doi: 10.1016/j.heliyon.2024.e35502. eCollection 2024 Aug 15.
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.
为评估18F- AlF- NOTA- RGD2正电子发射断层扫描（PET）/计算机断层扫描（CT）分子探针在小型猪肝纤维化无创分期中的疗效，揭示了一种侵入性诊断方法的潜在替代方案。本研究采用18F- AlF- NOTA- RGD2 PET/CT对小型猪进行成像以评估肝纤维化。方法包括分子探针的合成与质量控制、肝纤维化动物模型的建立、血清酶学检测、组织病理学检查、PET/CT成像、胶原蛋白含量与表达以及线粒体储备功能评估。18F- AlF- NOTA- RGD2 PET/CT分子探针有效区分了小型猪肝纤维化的不同阶段。血清酶学检测揭示了肝纤维化的不同阶段，随着纤维化进展，AST、ALT、TBIL和DBIL水平显著升高。值得注意的是，严重纤维化患者的ALT水平明显升高。胶原蛋白沉积逐渐增加以及α-SMA RNA表达和蛋白质水平升高有效区分了轻度和重度纤维化阶段。病理检查和天狼星红染色证实了这些发现，突出了胶原蛋白积累的大幅增加。PET/CT成像结果与组织病理学结果一致，表明放射性示踪剂摄取增加与纤维化严重程度相关。线粒体功能评估显示肝脏总谷胱甘肽含量和线粒体储备能力下降，尤其是在严重纤维化患者中。18F- AlF- NOTA- RGD2 PET/CT分子探针是一种用于肝纤维化无创评估的有前景的工具，在肝病学中比传统诊断方法具有潜在优势。
