核素-切伦科夫多模态显像关键技术研究

Based on the Cerenkov radiation(CR)which can produce the detectable optical signal, a new type of multimodality imaging by combining the radionuclide imaging and optical imaging with single radionuclide labeled probe is becoming the highlight of the molecular imaging recently. However the weak signal, poor tissue penetration, hardly three dimension construction or quantification of the Cerenkov optical signals limited its further developing. To resovle all above problems and fuse the radionuclide imaging with Cerenkov imaging is necessary in promoting multimodality imaging. .In this study we will explored the potential of using CR as a primary source of light to excite the rare-earth element which can produce stronger signal by absorbing the weak signal from CR(also named up-conversing), by doing so the signal of CR can be enhanced significantly. Differnent from those construction caculation based on homogeneous, we will also develop a new construction caculation based on heterogeneous which is close to the living organism. The quantification of the Cerenkov optical signal will be also analyzed followed by the three dimesion construction. Radionculide imaging with CT and Cerenkov optical imaging with CT will be acquired seperately, based on the space-match strategy the two seperated CT imaging will be matched firstly,followed by fusion of the radionuclide imaging and Cerenkov optical imaging. Radionulide and rare-earth element dual coupled NGR dimer peptide targeted on the angiogensis of the tumor is enrolled in tumor imaging to test and consummate the new establised radionuclide and Cerenkov multimodality fusion imaging method. .The ultimate destination of our this study is to estalblish a new platform for tumor early diagnosing, quantification and monitoring by detecting the molecule,function and anatomical changing of the tumor,the new multimodality imaging method of our this study will point out a new direction for the developing molecular imaging.

基于核素能够产生光信号的切伦科夫效应，核素标记探针可同时进行核素显像与切伦科夫光显像，成为备受关注的新型多模态显像方式。研究表明切伦科夫光显像存在信号弱、组织穿透性较差、难以进行三维重建与定量分析的不足，制约了核素切伦科夫多模态显像的发展。因此，如何有效增强切伦科夫光信号、实现光信号三维重建、定量分析及与核素信号的融合是发展核素切伦科夫多模态显像亟待解决的问题。本研究以核素切伦科夫光信号为初级光源激发稀土纳米颗粒，通过其上转换作用有效增强光信号；并创建基于深度补偿策略的光学非匀质三维成像新理论，实现切伦科夫光信号的重建与定量分析；采用异机CT影像空间配准，进行核素与切伦科夫光显像的有效融合。以核素稀土纳米颗粒双标记肿瘤新生血管靶向肽为探针，验证并完善核素切伦科夫多模态显像新方法，旨在从分子、功能与结构三个层面为肿瘤早期诊断提供准确而全面的在体、定量检测平台，开辟多模态分子影像研究新领域。

切伦科夫光学显像是重要的核素-光学多模态成像方式，但其面临信号强度弱、组织穿透差、难以三维重建和定量分析的挑战性问题。本研究在切伦科夫增强理论方面，发现并利用稀土掺杂纳米颗粒上转换发光原理及射线激发原理，实现了切伦科夫光信号在强度及穿透性上的显著增强，并提高了在体光学断层成像及肿瘤切除操作的准确性；在靶向探针方面，成功研发NGR系列分子影像探针，并系统改良68Ga核素标记技术，对NGR系列肿瘤新生血管探针标记多种核素及光学显像元件验证了其肿瘤靶向性；优化NGR探针结构，有效增强了该探针的肿瘤显像效果；在光学成像技术方面，创建切伦科夫光传输混合数学模型，提高了光学信号三维重建和定量分析的准确性；开发内窥切伦科夫荧光成像新技术，实现首例切伦科夫消化内镜的人体应用。