中文摘要
基底样乳腺癌(BLBC)恶度高、预后差,至今没有有效影像学诊断方法。本研究以BLBC多表达的两种抗原(EGFR、CK5/6)为分子靶标,以ER、PR、Her-2表达阳性为排除诊断,制备多个分子探针,实现上转换发光、核素及多模态显像,达到早期、特异诊断和鉴别BLBC的目的。首先创新应用三重态上转换发光显像,构建不同纳米上转换分子探针,将近红外光转化为四种不同颜色可见光,以颜色识别,实现无创、在体、可视化鉴别乳腺癌不同分子标记物表达;然后构建核素双靶标分子探针,以PET显像评估其对BLBC原发及转移灶诊断效能;最后通过核素标记纳米粒子,实现核素-上转换发光双模态、多靶点显像精确诊断BLBC。本研究构建纳米分子探针平台的思路,将可拓展用于多种恶性肿瘤的诊断和鉴别。需特别指出,研究应用三重态上转换发光显像,以不同颜色可见光识别不同分子标志物,颠覆常规影像诊断方式,必定在未来分子影像中起重要作用。
英文摘要
Basal-like breast cancer (BLBC) is a serious disease threatening to the women’s health with easily metastasis and poor prognosis. Until now, there have no efficicy imaging methods to diagnose BLBC. In this study, two antigens, EGFR and CK5/6, which are highly expressed in BLBC, will be chosen as molecular targets, while, ER, PR and Her-2 will be used to exclude the diagnosis of BLBC. Several molecular probes will be prepared, and upconversion luminescence (UCL), PET and multimodality imagings will be performed in order to early, specificly diagnosis and differencial diagnosis of BLBC. .Three parts will be included in this project. Firstly, four different nanoparticles will be prepared for triplet-triplet energy transfer (TTET) UCL. With different and simple color recognition, different molecular markers of breast cancer will be visulized noninvasively. Secondly, radionuclide labelled probe targeting EGFR and CK5/6 will be constructed for PET imaging. The primary and matastasis lesions will be evaluated in vivo. Lastly, nanoparticles for UCL will be labelled with radionuclide for nuclide and UCL multimodality imaging to precise diagnosis of BLBC. .The construction of different nanoparticles for molecular imaging in this study is not only for the diagnosis and differencial dignosis of breast cancer, but also could be extended to the application for other malignant tumors. Most importantly, an innovation TTET UCL platform makes it possible that different molecular markers could be identified by color visually, noninvasively and simply. This could share a totally new light on the conventional diagnostic methods, and must play an important role in molecular imaging.
