核素/红外二区双模特异SLN探针的构建及其靶向示踪机制的研究

Sentinel lymph node (SLN) is the first node or nodes in the lymphatic drainage of the primary tumor. The accuracy of the prediction of regional lymph node metastasis is as high as 95%, and less complications. Traditional tracers are mostly non-specific imaging agent and their poor localization restricts the further clinical application. The development of high spatial resolution/specific tumor SLN and mechanism analysis attracts researches great attention. We previously developed novel CD 20 antigen specific 99mTc-Rit which applied in more than 7000 cases SLN detection. Here we are aiming to build a dual-modality specific probe named 99mTc-Rituximab-CH1055, for real-time, in vivo, and molecular imaging of SLN using SPECT-CT/NIR-II technology. Mechanism: the dual-modality probe holds quantitative methods to describe CD20 antigen expression, is expected to be able to reveal the SLN specific /non-specific uptake ratio, and provide a theoretical basis for SLN specificity imaging; Clinical translation: with the SPECT-CT technology, it is expected to carry out deep tumor SLN detection and guide the intraoperative detection. In conclusion, the design of this new tracer intents to achieve a rapid and noninvasive detection of multiple tumor SLN, improve the quality of life of the patients.

前哨淋巴结（SLN）是原发肿瘤淋巴转移的第一站淋巴结，预测区域淋巴结转移的准确性高达95%。传统示踪剂多为非特异性显像剂，定位性差，使用要求高，临床推广有限。发展高空间分辨率、特异性肿瘤前哨淋巴结显影并进行示踪机制研究意义重大。本项目，在已有99mTc-Rit用于七千余例临床SLN探测基础上，以CD20为靶点，拟构建双模态特异性探针99mTc-Rituximab-CH1055，利用SPECT-CT/NIR-II技术实时、在体、分子水平探测前哨淋巴结。机制方面：该双模态探针本质是以受体定量的方式去阐述CD20抗原表达情况，有望能够揭示前哨淋巴结的特异性/非特异性摄取比例，为SLN特异性显像提供理论依据；临床转化方面：借助于SPECT-CT技术，有望进行深部肿瘤的SLN探测，并具有可引导术中探测和切除等显著优势，达到快速、无创检测多种肿瘤SLN的目的，改善患者生活质量。

前哨淋巴结（SLN）是原发肿瘤淋巴转移的第一站淋巴结，预测区域淋巴结转移的准确性高达95%。传统示踪剂多为非特异性显像剂，定位性差，使用要求高，临床推广有限。发展高空间分辨率、特异性肿瘤前哨淋巴结显影并进行示踪机制研究意义重大。项目研究期间，团队对核素/第二近红外窗口荧光染料和前哨淋巴结特异性分子探针的相互作用进行了充分研究，获得了核素/红外二区多模态特的特异性SLN分子探针，并在体外和动物层面上展现出良好的成像效果，为后续的临床转化奠定了基础。本研究在抗CD20的利妥昔单抗的基础上进行了化学偶联与修饰，将具有第二近红外窗口荧光性质的吲哚菁绿分子和具有单光子发射能力的锝-99m核素与之相连，获得了一系列针对SLN显像的分子探针，并在核医学与第二近红外窗口荧光模态上获得了满意的小鼠前哨淋巴结影像。在此基础上，进一步实现了正常光照条件下的小鼠前哨淋巴结可视化手术导航的实验。这一项目的成果有助于推动基于特异性抗体的前哨淋巴结显像在肿瘤诊断中的临床应用，为肿瘤外科的相关问题提供新的技术选项。