新型PET/NIRF双模态纳米探针的构建及其肿瘤靶向成像研究

分子探针的设计合成是分子影像学的核心。发展可以被多种成像模态同时检测到的、肿瘤靶向的分子探针是实现对微小肿瘤早期诊断的重要途径,是分子影像研究的一个关键科学问题。申请人前期研究已成功地合成了粒径大小约30 nm、不含有毒金属、RGD肽耦联的近红外荧光(NIRF,778nm)共轭聚合物纳米探针，该探针在小鼠体内的血流半衰期长达8小时，对高表达整合素αvβ3受体的脑胶质瘤U87MG有特异性的靶向效果。本项目拟在已有工作基础上，以乳腺癌为研究目标，结合NIRF成像的高灵敏度以及正电子发射断层(PET)成像对深度无限制的特点, 以NIRF共轭聚合物纳米材料为核层，放射性核素 F-18为壳层，构建新型的PET/NIRF核壳双模态纳米探针，并通过化学手段将RGD肽与PET/NIRF双模态纳米探针结合起来，构建更为有效的乳腺癌靶向的双模态分子探针。本项目的结果将为乳腺癌影像学早期诊断提供新方法。

The design and construction of molecular probes is the key in the application of molecular imaging. Developing effective, multi-modal, specific tumor-targeted molecular probes for early diagnosis of the smaller size tumor is necessary and timely. We have successfully developed an innovative RGD peptide coupling, near-infrared fluorescence (NIRF) nanoprobe with 30 nm in diameter last year. This novel probe contained no toxic metals, exhibited longer circulating time (half-life > 8 hours) and high serum stability, and produced strong near-infrared emission at 778 nm, and specific targeted to αvβ3 receptor hyper-expressed glioma in living mice. Based on our previous study, we purpose utilize the benefits from high sensitivity of NIRF imaging and unlimited depth penetration of positron emission tomography (PET) to develop a novel RGD-peptide coupling NIRF/PET associated-nanoprobe for targeted imaging breast cancer. This dual-modal nanoprobe will be more effective and more specific than old one, which was constructed using two critical parts: NIRF will be the core and F-18 will be the shell. The result of this study will provide a unique approach for the early diagnosis of breast cancer in vivo.