PET作为一种高灵敏度且无创的分子影像手段，广泛用于癌症的早期诊断及预后监测，开发特异性靶向癌细胞的PET探针具有十分重要的临床意义。CYP1B1在多种癌症中高表达，并且与乳腺癌的发生发展具有密切联系。本项目以CYP1B1为靶点，拟在其现有几类抑制剂分子骨架基础上进行探针的设计，采用不同的18F标记方法制备探针，通过不同的取代基或侧链调节探针的脂溶性，利用多种体内外实验对探针的稳定性、亲和力、脂溶性、特异性等进行评价，以期筛选出亲和力强、特异性高、成像效果好的18F标记PET探针，并用于乳腺癌Micro-PET-CT成像。进一步利用分子对接软件建立探针与CYP1B1蛋白的药效团模型，寻找可能的作用位点，为探针的进一步结构优化提供理论基础。此外，本项目拟开发高活性苯炔中间体、环醚以及18F-的三组分串联反应，通过该方法有望一步实现烷烃长链的引入以及18F标记，为这类探针的快速标记提供一种新方法。

As a highly sensitive and non-invasive molecular imaging method, PET is widely used in the early detection and prognostic monitoring of cancer. The development of PET probes that specifically target cancer cells has very important clinical significance. CYP1B1 is over-expressed in a variety of cancer and has a close relationship with the occurrence and development of breast cancer. This project takes CYP1B1 as the target and intends to design probes based on the molecular skeletons of several existing CYP1B1 inhibitors. Different 18F labeling methods will be used to prepare the probes, and the lipolysis will be adjusted by different substituents or side chains. The stability, affinity, liposolubility, and specificity of the probes will be evaluated through various in vivo and in vitro experiments, in order to screen out the 18F labeled PET probes having good imaging effect, high selectivity and affinity with CYP1B1. The selected one or more probes will be used for breast cancer Micro-PET-CT imaging. Further, we will use the molecular docking software to establish the pharmacophore model of the probes and CYP1B1 protein, to find possible active sites, and to provide a theoretical basis for further structural optimization of the probes. In addition, we intend to develop a three-component tandem reaction of highly reactive benzyne with cyclic ethers and 18F- in this project. This method is expected to achieve the introduction of alkyl long chains and 18F labeling in one step, providing a rapid method for the labeling of such probes.