新型胰岛β细胞分子探针的构建及胰岛功能显像的实验研究

项目名称： 新型胰岛β细胞分子探针的构建及胰岛功能显像的实验研究

项目编号： No.81471691

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 万卫星

作者单位： 江南大学

项目金额： 73万元

中文摘要： 糖尿病是临床上最常见的内分泌疾病之一，在我国发病率仍然保持持续上升的趋势，胰岛移植为糖尿病患者带来治疗的新希望，但是目前缺乏有效手段在移植胰岛大量丢失前早期发现移植胰岛的排斥反应和炎症。临床上迫切需要建立无创、有效的方法对体内β细胞的量进行精确的测量，动态监测β细胞量的变化以评价病情进展和治疗效果。GLP-1R和PROKR1是胰岛β细胞显像的非常有潜力的分子靶点，现有研究尽管取得一定的进展，但是距离临床使用还是存在一定的距离。本研究将建立糖尿病动物模型和胰岛移植的动物模型，利用正电子核素18F标记PROKR1配体和GLP-1R的分子探针，对β细胞的量进行动态监测，实现活体、实时的定量检测体内β细胞量，其可靠性以病理及免疫组化检查加以证实，从而建立一种新的分子显像方法，能够有效的用于胰岛β细胞的定量、动态监测，解决目前临床上存在的难题。

中文关键词： 胰岛；β细胞；分子探针；正电子发射断层显像

英文摘要： Diabetes is one of the most common endocrine diseases in clinical, it's incidence in our country still keep rising. Islet transplantation has brought a new hope for the treatment of patients with diabetes. At present, there has no effective means to detect islet allograft rejection and inflammation before mass loss of allograft. It is urgent to find a non-invasive and effective method; it can evaluate the disease progression and therapeutic effect by accurate measuring and dynamic monitoring the change of β cell mass in vivo. GLP-1R and PROKR1 is the promising molecular target of β cell. The current research made some progress, but there is some distance from the clinical use. This project will use the positron radionuclide 18F to label PROKR1 ligand and GLP-1R, PET imaging will performed in rat models with diabetic or islet transplantation for a real-time quantitative detection β cell mass and dynamic change in vivo. Its reliability will be confirmed by pathological and immunohistochemical examination. To establish a new method of molecular imaging, which can be effectively, used for the quantitative detection and dynamic monitor the change of β cell mass, it is helpful for solving the problem currently existing in the clinic.

英文关键词： pancreatic islet;βcell;molecular probe;positron emission tomography