Yao Shaobo, Xing Haiqun, Zhu Wenjia, Wu Zhanhong, Zhang Yingqiang, Ma Yanru, Liu Yimin, Huo Li, Zhu Zhaohui, Li Zibo, Li Fang
Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China.
Department of Radiology and Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, NC 27599, USA.
Nucl Med Biol. 2016 Mar;43(3):206-14. doi: 10.1016/j.nucmedbio.2015.11.008. Epub 2015 Dec 4.
The noninvasive imaging of bacterial infections is critical in order to reduce mortality and morbidity caused by these diseases. The recently reported (18)F-FDS ((18)F-2-fluorodeoxy sorbitol) as a PET (positron emission tomography) tracer can be used to image Enterobacteriaceae-specific infections and provides a potential alternative to this problem compared with other probes for imaging infections. In this study, automatic synthesis, validation of (18)F-FDS and a first-in-human study were performed and discussed.
A multifunctional synthesis module was employed for the radiosynthesis of (18)F-FDG ((18)F-2-fluorodeoxy glucose) and (18)F-FDS starting from (18)F ion using two-pot three-step fully automated reactions. The behavior of (18)F-FDS as an in vivo imaging probe for infections was evaluated in an Escherichia coli mouse infection model. The first detailed pharmacokinetic and biodistribution parameters were obtained from healthy human volunteers.
The uptake of (18)F-FDS in an E. coli mouse-myositis infection model was easily differentiated from other organs and normal muscle. Intensive lesion uptake declined after antibiotic treatment. In the pilot human study, no adverse effects due to (18)F-FDS were observed up to 24 h post-injection. The radiotracer was rapidly cleared from the circulation and excreted mainly through the urinary system.
We conclude that (18)F-FDS PET holds great potential for appropriate and effective for the imaging of bacterial infections in vivo. These preliminary results indicate that further clinical studies are warranted.
细菌感染的无创成像对于降低这些疾病所致的死亡率和发病率至关重要。最近报道的(18)F-FDS((18)F-2-氟脱氧山梨醇)作为一种正电子发射断层扫描(PET)示踪剂,可用于对肠杆菌科特异性感染进行成像,与其他感染成像探针相比,为解决这一问题提供了一种潜在的替代方法。在本研究中,进行并讨论了(18)F-FDS的自动合成、验证以及首次人体研究。
采用多功能合成模块,从(18)F离子开始,通过两罐三步全自动反应进行(18)F-FDG((18)F-2-氟脱氧葡萄糖)和(18)F-FDS的放射性合成。在大肠杆菌小鼠感染模型中评估了(18)F-FDS作为感染体内成像探针的行为。从健康人类志愿者中获得了首个详细的药代动力学和生物分布参数。
在大肠杆菌小鼠肌炎感染模型中,(18)F-FDS在病变部位的摄取很容易与其他器官和正常肌肉区分开来。抗生素治疗后,病变部位的强烈摄取下降。在人体初步研究中,注射后24小时内未观察到因(18)F-FDS引起的不良反应。该放射性示踪剂迅速从循环中清除,主要通过泌尿系统排泄。
我们得出结论,(18)F-FDS PET在体内细菌感染成像方面具有适当且有效的巨大潜力。这些初步结果表明有必要进行进一步的临床研究。