Synthesis And Application Of Mixed β-Diketonate-Lanthanide Complex-based Bimodal Probes For Optical And Magnetic Resonance Imaging

Bimodal optical-magnetic resonance imaging technology,which integrates advantages of optical imaging（OI）technique（high sensitivity and selectivity）with that of magnetic resonance imaging（MRI）technique（high spatial resolution and deep tissue penetration）,has exciting potentials and attracted a lot of research interests.It can visualize biological target objects or biological events in vivo at physiological,cellular,and molecular levels,which provides both abundant anatomical and molecular information for biomedical research and clinical diagnosis.In this thesis,mixedβ-diketonate-lanthanide complex-based bimodal probes for OI/MRI were designed and synthesized.And they were successfully applied for recognition of biomacromolecule,as well as time-gated luminescence（TGL）/MR imaging of them.The development of these probes can solve the bottleneck problem of dual-mode probe that their preparation is difficult,enriches dual-mode OI/MRI probe,and provides a powerful tool for the development of biological imaging technology and clinical application.Firstly,β-diketonate-lanthanide complexes,BHHBCB-Eu³⁺（TGL signal group）and BHHBCB-Gd³⁺（MR signal group）were conjugated with a tumor-targetable biomacromolecule,transferrin（Tf）to construct the probes,Tf–BHHBCB–Ln³⁺,for TGL and MR imaging of cancerous cells in vitro and in vivo.The as-prepared probes possess strong red luminescence with a long lifetime（t=0.52 ms,f=0.40）,excellent longitudinal relaxivity(r₁=35.67 mM^-1s^-1),outstanding biocompatibility,water solubility and stability.Besides they show high specificity to bind with the transferrin receptor-overexpressed cancerous cells.The practicability of Tf–BHHBCB–Ln³⁺has been roundly estimated by TGLI of cultured cancerous cells and cryosectioned tumor slices,as well as the tumor-targeting T₁-weighted MRI of tumor-bearing mice.Based on the previous finding thatβ-diketonate-gadolinium complex exhibited remarkably high longitudinal and transverse relaxivities after it was covalently bound to biomacromolecule,dual-modal probes,BT-BHHBCB-Ln³⁺(Ln³⁺=Eu³⁺/Gd³⁺),has been designed and synthesized for recognition and TGL/MR imaging of avidin.It was constructed by conjugatingβ-diketonate-lanthanide complexes,BHHBCB-Ln³⁺(Ln³⁺=Eu³⁺/Gd³⁺)with biotin.Based on high specific biotin-avidin interaction,BT-BHHBCB-Eu³⁺can recognize and fluorescently label avidin,and BT-BHHBCB-Gd³⁺shows turn-on MR response to avidin.A mixture of BT-BHHBCB-Eu³⁺/Gd³⁺can be used for dual-modal TGL/MR detection of avidin in vitro and in vivo.