中文摘要
一氧化氮是一种重要的生物信使分子和生理标志物。NO的浓度异常与多种疾病的发生发展,如炎症,癌症,器官移植排异,二型糖尿病,老年痴呆病等密切相关。利用NO正电子显像剂进行PET成像从而精确地对NO开展活体成像,并指导NO浓度的调节可以有效地在这些炎性疾病早期发现病灶、控制病程,是临床医生和药物研发工作者急需的影像检测手段。本项目拟设计、合成并评价基于二氢吡啶骨架结构的NO正电子显像剂,开发对NO高特异性和高灵敏度的18F标记的小分子PET显像剂。利用能够进行定量检测的PET探测18F标记的显像剂分子在只有NO的参与下才在体内发生碳碳键断裂反应来反映活体NO的数量或浓度及分布。这一新型的NO影像检测手段将克服荧光、化学发光、电子顺磁共振、核磁共振等已有的NO成像方式无法进行活体成像或者灵敏度不足等缺点,实现高特异性和高灵敏度的NO活体成像,推进NO在相关疾病中的作用的研究。
英文摘要
Nitric Oxide is an important biologically messenger molecular and biomarker, whose concentration is highly related with occurance and development of many diseases, such as inflammation, cancer, organ transplant rejection, Type 2 diabetes and Alzheimer's disease. Since PET imaging performed using NO sepecific probes can not only locate the abmornal lesions effectively, detect NO concentration accurately in vivo, but also guide the NO concentration regulation therapy, PET imaging probes of NO is highly desirable in both pharmacutical research and clinical practice. This project focuses on design, synthesis and evaluation of novel small molecular NO PET probes based on the scaffold of dihydropyridine structure in order to imaging NO in vivo with high specificity and high sensitivity. The 18F labeled intermediates produced during carbon-carbon bond cleavages,which can only triggered by NO, would be detected quantitatively by PET to reflect the NO concentration and distribution. This new imaging method may overcome the shortcomings of existing NO imaging method such as fluorescence, chemiluminescence, EPR and MR, and help to unveil the NO mechanism in those related diseases.
