新型PET与活性氧响应的NIR-II区荧光成像双模态分子探针的制备与性能研究

如何对恶性肿瘤进行早期精准诊断、精准手术导航和检测肿瘤内特征分子变化，是提高肿瘤患者生存质量和治愈率的关键。因此发展一种分子探针能够同时满足上述需求是目前的研究热点。为解决这一问题，本课题拟构建一种靶向整合素的肿瘤内活性氧响应的近红外二区荧光与 PET 双模态成像分子探针，用于肿瘤的早期精准诊断、精准手术导航、肿瘤内活性氧检测以及疗效评价。该分子探针结合了近红外二区荧光成像的微米级高空间分辨率、肿瘤内活性氧响应性和PET的高穿透深度及可定量检测的优势。两种影像的优势互补可以实现一次注射分子探针完成精准肿瘤成像定位和精准手术导航，减少手术过程中微小病灶的遗漏，也可以为肿瘤发展过程中活性氧变化提供精准的影像信息。此外，该分子探针还可以用于肿瘤术后复发监测和化疗疗效监测。该双模态分子探针将为肿瘤的诊断和治疗提供更加丰富的影像信息，为设计新型多功能分子探针提供一种新的研究思路。

The early precise diagnosis, accurate surgical navigation and detection of characteristic molecules in variety of malignant tumor are the vital to improve the quality of life and cure rate of cancer patients. Therefore, it is necessary to develop an ideal molecular probe which can simultaneously meet all the mentioned requirements. To address this issue, in this project, we will construct an αvβ3 -targeted dual-modal positron emission computed tomography (PET) and second near-infrared window (NIR-II) fluorescence molecular probe to achieve early cancer diagnosis, precise surgical navigation, imaging of reactive oxygen species (ROS) and evaluation of therapeutic effect of tumor. The molecular probe integrates the advantages of NIR-II fluorescence imaging with a high spatial resolution at the micrometer scale, a high response of ROS in tumor into the advantages of PET with a high penetration depth and absolute quantitative analysis, hence achieving complementary advantages. Owing to the excellent capacity for tumor detection and delineation of probe, preoperative tumor detection and intraoperative image-guided surgery of tumor can be realized by administering once, which can effectively avoid omission of minor lesions and wrong diagnostics of tiny tumor. Meanwhile, it can be applied for accurate detection and imaging of ROS in tumor. In addition, the probe can also be used to monitor the postoperative recurrence of tumor and the therapeutic effect of cancer chemotherapy. The dual-modal molecular probe will provide rich abundant image information for the diagnosis and treatment of tumor, and pave a new way for the design of new multifunctional molecular probes.