68Ga-siderophores PET显像在侵袭性肺部真菌病早期诊断中的实验研究

Invasive pulmonary fungal infection ( IPD ) in the immunocompromised patients is a major infective cause of morbidity and mortality. The mortality associated with IPD remains high, mainly due to the difficulties and limitations in diagnosis. The incidence of IPD has increased significantly in recent years in China. Early diagnosis and effective treatment is critical to a favorable outcome of IPD but is difficult to achieve with currently available diagnostic tools. 68Ga-siderophores PET imaging technology provides the possibility for the early diagnosis of IPD. Iron plays an essential role in fungal virulence and the host immune function. Part of the infection process can, therefore, be regarded as a battle for iron between host and pathogen. To succeed in this battle, the invading pathogen produces siderophores，together with highly efficient siderophore transporters to compete for the iron of the host. 68Ga is a positron emitter with complexing properties comparable to those of Fe, has a wide application prospect in the inflammatory lesions in PET imaging. Therefore, we attempted to use the same siderophores radiolabeled with 68Ga as Trojan horses to allow specific imaging of the infection process.This project aims to preparing one kind of 68Ga-siderophore candidates for the specific detection of Aspergillus, evaluate the value in early diagnosis of IPD in vitro and in vivo. we attempted to use the same siderophores radiolabeled with 68Ga as Trojan horses to allow specific imaging of the infection process. It has important value in the early detection of IPD.

侵袭性肺部真菌病(IPD)多发于免疫功能受损人群，病死率高。近年来我国IPD的发病率明显上升。早期诊断、有效治疗是降低其病死率的关键。然而，目前尚缺乏有效的早期诊断方法。68Ga-siderophores PET显像技术为早期诊断IPD提供了可能。铁与致病微生物毒力密切相关。致病微生物通过合成和分泌铁螯合剂siderophores来争夺宿主体内的铁，并通过包膜上特异性受体转运到体内。68Ga可以替代铁与siderophores稳定结合，在炎症病灶PET显像中具有广泛应用前景。本项目拟制备针对曲霉菌特异68Ga-siderophores分子显像剂，通过动物实验评价其在IPD早期诊断中的价值。拟制备的68Ga-siderophores分子显像剂可以作为特洛伊木马被真菌摄取，因此在IPD早期诊断上具有重要价值。

侵袭性肺部真菌病(IPD)多发于免疫功能受损人群，病死率高。然而目前尚缺乏有效的诊断方法。我们课题组制备了曲霉菌特异68Ga-TAFC分子显像剂，该显像剂的放射化纯度可达到99%，进而通过曲霉菌大鼠模型的PET显像，分析了曲霉菌感染病灶对的68Ga-TAFC特异性摄取及体内生物学分布。研究显示68Ga-TAFC在放射性标记和代谢稳定性方面具有优势，可以作为“特洛伊木马”被烟曲霉菌摄取后可以在PET下清晰地显示出炎症病灶，病灶部位放射强度与感染程度密切相关，具有很高的敏感度。本研究显示了68Ga-TAFC在曲霉菌感染诊断中的巨大潜力，需要进一步完善和深化，亦需要更多资金的支持。.关键词：侵袭性肺真菌病；PET；68Ga-TAFC