Study On The Enhanced Luminescence Imaging Of Rare-earth Fluoride Nanocrystals With Core-shell Structure Excited By Nuclide ?-radiation

The combination of radionuclides with nanoparticles has been widely used in various biomedical researches,including disease diagnosis and treatment.This combination not only can directly carry out traditional PET,SPECT and CL imaging,but also can realize in vivo activated optical imaging/therapy in deep tissues.These new type of imaging and treatment are based on the characteristic X-rays from the interactions between nuclides and nanomaterials.Therefore,the purpose of this paper is to investigate the enhanced luminescence imaging of core-shell rare-earth fluoride nanocrystals excited by nuclide radiations,by applying the inherent and emerging properties from the interactions of nuclide radiations and nanoparticles.The research of this paper will provide some experimental basis for the new applications of nuclide-labeled rare-earth nanocrystals in the field of biomedicine,such as imaging of tumor and lymph nodes as well as the related imaging-guided surgical resection.In this paper,core-shell rare-earth fluoride nanocrystals were designed and prepared,and the structure characterization,property analysis and small-animal optical imaging and SPECT/CT imaging of lymph nodes as well as mapping-guided surgical resection were studied.The main contents of this paper are as follows:In the first chapter,the influencing factors of in vivo applications of nanoparticles,the nanoparticle-based radiotracers and the applications in the nuclear imaging,the interactions between nanoparticles and radionuclides and the related novel imaging are briefly reviewed.In the end,the subject and content of the thesis are summarized.In second chapter:Fluoride nanocrystals with different rare earth elements and the corresponding core-shell nanocrystal NaGdF₄:15%Eu@NaLnF₄?Ln=Y,Gd,Lu?were synthesized by using solvothermal method.The serial characterization and analysis showed that the synthesized nanocrystal had uniform size,good dispersion and quasi-spherical structure.In the third chapter:the research contents of this part were to investigate in vitro and in-vivo luminescence imaging by using?-ray radiation of nuclide ^99mTc to excite core-shell rare-earth fluoride NaGdF₄:15%Eu@NaLnF₄?Ln=Y,Gd,Lu?,and to explore its influencing factors and possible mechanism.First,for the core?-NaGdF_ee:X%Eu³⁺?X=1%,5%,15%,30%?nanocrystals,we conducted an experiment on the optical properties from the excitation of ultraviolet and nuclides.The results showed that the doping concentration of Eu³⁺could influence the emission intensity of?-NaGdF₄:X%Eu³⁺nanocrystals,and reached the highest when the concentration of Eu³⁺was 15%.Furthermore,we carried out the fluorescence spectrum and the radiation-emission spectrum of?-NaGdF₄:X%Eu³⁺nanocrystals.The results showed that the radiation-emission spectrum of?-NaGdF₄:X%Eu³⁺was consistent with the emission peak position of the conventional fluorescence spectrum,sharing the same intensity variation rule,also holding the phenomenon of energy transfer and higher energy excitation.Taking use of the above-mentioned optical experimental methods,the optical properties and spectral data analysis of core-shell rare-earth fluoride nanocrystals were further carried out.The results showed that the light-emitting effect of the core-shell nanocrystal NaGdF₄:15%Eu@NaLnF₄ was better than that of the core material.More importantly,nuclide?-ray excited radioluminescence experiments showed that core-shell nanocrystals with high atomic number could generate the characteristic X-ray and re-excite the inner core so as to enhance the radiation emission.On the basis of the above-mentioned experimental results,we carried out the optical and SPECT/CT multi-modal imaging of sentinel lymph node by injecting core-shell nanocrystals NaGdF₄:15%Eu@NaLnF₄ into the mice body,and also the imaging-guided lymph node resection operation.In summary,our research results showed that the further excitation of the secondary characteristic X-ray produced by nuclide?-ray-excited NaGdF₄:15%Eu@NaLuF4 nanocrystal could realize the enhanced luminescence imaging,combining with the SPECT/CT image,it not only could realize the localization imaging of the sentinel lymph node and the imaging guidance removal,but also greatly promote the combined application potentials of nuclides and rare-earth fluoride nanomaterials,including various biomedical fields such as chemical sensor,biological imaging and photodynamic therapy.