新型胃癌血管靶向探针PEG-(GX1)2的制备及用于胃癌早期诊断的研究

Gastric cancer is seriously endangering the health of Chinese people. It is the major disease that our country have to overcome independently. However, it is difficult to achieve early diagnosis with existing technologies. Cerenkov luminescence endoscopy is an emerging hybrid modality that combined molecular imaging with endoscopic techniques, providing a new technical method to solve this problem. It uses optical imaging devices to detecting the signals of radionuclide probes, and it is able to detect the gastrointestinal system and other cavities. It has more advantages than conventional optical imaging modalities. But there is yet no specific targeting probes for gastric cancer imaging. We had found a peptide GX1 (CGNSNPKSC) binding to vasculature endothelial cells of human gastric cancer. The biological properties of GX1 has been greatly improved by chemical modification. The project intends to continue to make use of chemically modified GX1 to prepare positron probe 68Ga-NOTA-PEG-(GX1) 2, and validates its specificity and targeting ability of gastric cancer both in vitro and in vivo．Then we will establish Cerenkov luminescence endoscopy system and observe the position of the probe in the mouse model of gastric cancer in situ and evaluate diagnostic consistency with the Nano PET / CT．This study was designed to provide a theoretical basis for early diagnosis of gastric cancer with applications of the Cerenkov endoscopic and GX1 peptide, and provide a new strategy and a new method for the early diagnosis of gastric cancer．

胃癌严重危害国人健康，是我国必须自主攻克的重大疾病，然而现有技术难以实现其早期诊断。新出现的切伦科夫内镜将分子影像学与内镜技术相结合，为解决这一难题提供了新的技术手段，它是利用光学成像设备检测放射性核素探针的信号，并可以探测胃肠道等腔道系统，解决了光信号穿透力弱的问题，但目前胃癌尚缺乏特异性的靶向探针。前期工作中，我们筛选出了能与胃癌血管内皮细胞特异性结合的短肽GX1，并且对其进行了化学修饰，大大提高了它的生物性能。本项目拟继续利用化学方法修饰GX1，进而制备正电子核素探针68Ga-NOTA-PEG-(GX1)2，并对其体内外鉴定，验证探针对胃癌的特异性和靶向性；自主搭建切伦科夫内镜荧光成像系统，性能测试后观察探针在胃癌原位模型鼠体内定位，并与Nano PET/CT对比诊断的一致性。本研究旨在为切伦科夫内镜的应用及GX1用于胃癌的早期诊断提供理论依据，为胃癌早期诊断提供新策略与新方法。

胃癌严重危害国人健康，是我国必须自主攻克的重大疾病，然而现有技术难以实现其早期诊断。新出现的切伦科夫内镜将分子影像学与内镜技术相结合，为解决这一难题提供了新的技术手段，它是利用光学成像设备检测放射性核素探针的信号，并可以探测胃肠道等腔道系统，解决了光信号穿透力弱的问题，但目前胃癌尚缺乏特异性的靶向探针。前期工作中，我们筛选出了能与胃癌血管内皮细胞特异性结合的短肽GX1，并且对其进行了化学修饰，大大提高了它的生物性能。本项目利用化学方法修饰GX1，制备了正电子核素探针68Ga-DOTA-KEK-(GX1)2，并对其进行了体内外鉴定，验证了探针对胃癌的特异性和靶向性；自主搭建了切伦科夫内镜荧光成像系统，并对其改良和参数校准，且首先在临床中应用。本研究为切伦科夫内镜的应用及GX1用于胃癌的早期诊断提供了理论依据，为胃癌早期诊断提供了新策略与新方法。