18F标记反义寡核苷酸一体化ToF-PET/MR成像在肝纤维化早期诊断的临床前期研究

肝纤维化的早期诊断和精准分期，对肝病防治至关重要。前期研究发现，甲状腺素转运蛋白(TTR)、间α胰蛋白酶抑制剂重链H1(ITIH1)、丝氨酸蛋白酶抑制剂分支F2(SERPINF2)、水通道蛋白(AQP)是肝炎转化为肝纤维化的四个关键基因，其中TTR及AQP关系最密切。项目组的前期研究证实了AQP在纤维化进程的特异性表达，并验证了AQP分子成像在诊断肝纤维化的可行性；同时成功进行了TTR基因的分子病理研究和反义基因显像。本项目拟(1)先明确血及肝组织细胞的四种基因表达水平与肝纤维化的关系，建立分子病理分型模型；(2)再优化PET的[18F] FB-HYNIC-TTR-ASO示踪剂标记方法，确定TTR分子靶向成像的流程；(3) 最后采用一体化ToF-PET/MR进行TTR及AQP分子靶向成像，明确影像定量数据与基因表达的相关性，实现肝纤维化的精准定量诊断，为肝纤维化的基因水平诊治提供理论依据。

Early detection and accurate staging of liver fibrosis are important for the liver disease prevention and control. Previous studies have found that TTR, ITIH1, SERPINF2 and AQP are four key genes to the transformation from hepatitis to liver fibrosis, while TTR and AQP are closely related to the early liver fibrosis. The previous research confirmed the specific expression of AQP in the process of fibrosis, verified the feasibility of molecular imaging in the diagnosis of early liver fibrosis, and also succeed in the molecular pathology research of TTR and the antisense gene imaging. This project intends to (1) firstly, establish the relationship between the expression level of these four genes in blood and hepatocyte and the liver fibrosis, set up the molecular pathological staging model; (2) secondly, optimize the [18F] FB-HYNIC-TTR-ASO tracer marker method of PET, to establish the operation process of TTR targeted molecular imaging; (3) at last, with the integrative ToF-PET/MR on TTR and AQP targeted molecular imaging, get the correlation of imaging quantitative data and the gene expression, to realize the accurate quantitative diagnosis of liver fibrosis, achieve the individualized diagnosis and treatment for liver fibrosis at gene level.