死亡受体5靶向分子探针89Zr-CTB006的构建及其在PET免疫显像中的研究

死亡受体5（DR5），也称肿瘤坏死因子相关凋亡诱导配体受体2（TRAIL-R2），因其选择性地肿瘤细胞杀伤作用成为肿瘤治疗的热门靶点。多项临床试验显示其靶向治疗在部分患者中表现出显著的抗肿瘤效果，但II期临床试验却均未取得预期成功。表明其在未筛选患者中的临床试验难以成功，亟需探索一种筛选获益患者的有效方法。本项目使用新型长半衰期核素Zr89标记其特异性抗体CTB006构建靶向分子探针89Zr-CTB006，在细胞水平对其对DR5的靶向特异性、作用关系及表达水平的定量进行研究。并通过PET/CT的高分辨及定量等能力，对其定量检测DR5表达的能力进行验证。总之，本项目构建的分子靶向探针，从分子水平，可验证DR5单抗与其结合的特异性，并获得其激动细胞凋亡的相关作用机制；从肿瘤临床免疫显像方面，可提供肿瘤DR5表达水平的无创性定量检测方法，指导DR5靶向肿瘤治疗中获益患者筛选。

Death receptor 5 (DR5), also known as tumor necrosis factor related apoptosis inducing ligand receptor 2 (TRAIL-R2), has become a hot target of tumor therapy because of its selective killing effect on tumor cells. A number of clinical trials showed that DR5 targeting therapy showed significant antitumor effect in some patients, but no phase II clinical trials succeed. Therefore, it is difficult to succeed in clinical trials without screening patients and it is urgent to explore an effective method for screening patients who would benefit from DR5 targeting therapy. In this research, we would use a new long half-life nuclide 89Zr to label DR5 specific antibody CTB006 to construct a DR5 targeting molecular probe 89Zr-CTB006. And its targeting specificity, functional relationship and DR5 expression levels would be studied at the cell level. The ability of PET / CT to detect DR5 expression would be verified with its high resolution and quantitative ability. Take together, the molecular targeted probe constructed in this project would verify the specificity of DR5 monoclonal antibody and its combination at the molecular level, and obtain the relevant mechanism of its activation of apoptosis. From the aspect of tumor clinical immunoimaging, it would provide a non-invasive quantitative detection method of DR5 expression levels in tumor lesions and screening of patients who would benefit from DR5 targeted antitumor treatment.