18F-3PRGD2 PET-MR分子成像在肝脏纤维化早期诊断研究

arlier, the quantitative diagnosis of liver fibrosis in the early treatment, efficacy evaluation has important value. So far, CT, MRI and ultrasound imaging technology can only be found in advanced liver fibrosis lesion. Noninvasive detection of early liver fibrosis and the stage of research are rarely used for molecular imaging techniques. Our previous research focused on using 99mTc-3PRGD2 as the early liver fibrosis probe using SPECT imaging for diagnosis of liver fibrosis in stage I and stage II, and achieve a breakthrough. However, the SPECT device detection sensitivity and resolution is much lower than that in PET, and cannot be accurately quantitative. The study on the basis of our previous work, for the first time using 18F-3PRGD2 as probe, the use of free tissue integration of ionizing radiation with imaging quantitative diagnosis of early liver fibrosis TOF function of PET-MRI equipment. Synthesis of 18F-3PRGD2 probe, liver fibrosis model of liver fibrosis, detected in different stages of 18F-3PRGD2 in mice liver quantitative uptake, as well as the relationship between the molecular pathologic results, to achieve the early quantitative diagnosis of early liver fibrosis (stage I and stage II disease).

早期、定量化诊断肝脏纤维化对于其早期治疗、疗效评价均具有重要的价值。迄今，CT、MRI和超声影像技术仅仅能够发现肝脏纤维化中晚期病变。采用分子影像技术无创检测肝脏早期纤维化、并对其分期的研究很少。我们先前研究主要集中在采用99mTc-3PRGD2作为肝脏早期纤维化探针使用SPECT进行成像对肝脏纤维化I期和II期进行诊断，并取得突破性进展。但是，SPECT设备检测灵敏度和分辨率远远低于PET，并且无法进行精确定量。本研究在先前工作的基础上，首次采用18F-3PRGD2作为探针，使用对组织无电离辐射的一体化具有TOF功能PET-MRI设备进行成像对早期肝脏纤维化进行定量化诊断。合成18F-3PRGD2探针后，大鼠肝脏纤维化模型上进行研究，检测在不同肝脏纤维化阶段18F-3PRGD2在大鼠肝脏定量摄取，以及与分子病理结果之间的关系，期待达到早期定量化诊断早期肝脏纤维化（I期和II期病变）。

在18F标记3PRGD2标记多肽基础上，创立采用18F-FDG直接一步法标记RGD多肽方法。按照已有方法建立大鼠肝脏纤维化模型，并且建立采用PET-MR扫描大鼠模型和进行定量分析的流程与方法。18F标记3PRGD2和18F-FDG-RGD标记率分别为185%和205%。大鼠肝脏纤维化模型组30分钟时肝/心脏比值明显高于对照组。该研究结果表明18F-RGD肝脏整合素受体成像对肝脏纤维化早期诊断具有重要价值，MRI图像为PET定量分析提供了清晰地解剖结构，多b值DWI对于大鼠模型肝脏纤维化诊断具有参考价值。