Chemistry of multimodal imaging tools for image guided surgery in glioblastoma

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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.