Chemistry of multimodal imaging tools for image guided surgery in glioblastoma

该项目旨在利用生物结合的量子点来特定靶向胶质母细胞瘤肿瘤和实时荧光成像；这可能会应用于辅助外科医生在术中切除肿瘤。此外，还将研究量子点作为多模式成像工具在胶质母细胞瘤的术前成像(例如MRI/PET)中的潜在用途。在本项目中，将利用最近建立的可见光和近红外荧光发射方法来合成InP/ZnS核/壳量子点和银基量子点。有机方法将被用来合成针对胶质母细胞瘤的生物相关分子，例如，当PSMA在胶质母细胞瘤中过表达时，基于PSMA-11的PSMA靶向基序可能被用来连接到量子点。其他已建立的针对胶质母细胞瘤的靶点也可以使用，例如抗体和其他基于短肽的药物。量子点与特定结合分子的功能化是通过基于聚乙二醇基的连接物，并最终在量子点表面加入基于Gd的络合物和Ga-68。在该项目中，定期对已制备的化合物进行表征。量子点通过UV-Vis、DLS和荧光进行表征；合成的分子通过TLC、核磁共振、LC MS、IR和元素分析进行表征。将通过流式细胞术和基于显微镜的方法对胶质母细胞瘤细胞系(例如U87 MG细胞)进行评估。对于核磁共振等术前方法，材料的松弛程度将通过使用核磁共振扫描仪来发现，并用于获得图像。依赖于胶质母细胞瘤细胞的成功特异性摄取，临床前实验可能在胶质母细胞瘤小鼠模型上进行。

This project aims to utilise quantum dots that are bioconjugated to specifically target glioblastoma tumours and real-time fluorescence imaging; this may be applied to aid surgeons in intraoperative tumour resections. Furthermore, the potential use of quantum dots as multimodal imaging tools for preoperative imaging (e.g. MRI/PET) of glioblastoma will be studied. In this project, synthesis of InP/ZnS core/shell quantum dots and Ag-based quantum dots will be carried out using recently established methods for fluorescence emission in visible and near infrared regions. Organic methods will be utilised to synthesise biologically relevant molecules for specific targeting of glioblastoma e.g. as PSMA is overexpressed in glioblastoma a PSMA-targeting motif based on PSMA-11 may be utilised to conjugate to the quantum dot. Other established targets for glioblastoma may also be used e.g. antibodies and other short peptide based drugs. Functionalisation of the quantum dot with the specifically binding molecule is through a PEG based linker and eventually incorporation of Gd-based complexes and Ga-68 on the surface of the quantum dot. Characterisation of prepared compounds is carried out regularly in the project. Quantum dots are characterised through UV-Vis, DLS and fluorescence; synthesised molecules are characterised through TLC, NMR, LCMS, IR and elemental analysis. Evaluation will be carried out in glioblastoma cell lines (e.g. U87MG cells) through flow cytometry and microscopy based methods. For preoperative methods such as MRI, the relaxivity of the material will be found with the use of NMR scanners and used to obtain images. Dependent on the successful specific uptake in glioblastoma cells, preclinical experiments may be carried out on glioblastoma mouse models.