Li Xiang-Guo, Hagert Cecilia, Siitonen Riikka, Virtanen Helena, Sareila Outi, Liljenbäck Heidi, Tuisku Jouni, Knuuti Juhani, Bergman Jörgen, Holmdahl Rikard, Roivainen Anne
Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, FI-20520 Turku, Finland; Turku PET Centre, Åbo Akademi University, Kiinamyllynkatu 4-8, FI-20520 Turku, Finland.
Medical Inflammation Research, Medicity Research Laboratory, University of Turku, FI-20520 Turku, Finland; The National Doctoral Programme in Informational and Structural Biology, Tykistökatu 6, FI-20520 Turku, Finland.
ACS Med Chem Lett. 2016 May 16;7(9):826-30. doi: 10.1021/acsmedchemlett.6b00160. eCollection 2016 Sep 8.
Recently mannan from Saccharomyces cerevisiae has been shown to be able to induce psoriasis and psoriatic arthritis in mice, and the phenotypes resemble the corresponding human diseases. To investigate the pathological processes, we set out to label mannan with fluorine-18 ((18)F) and study the (18)F-labeled mannan in vitro and in vivo with positron emission tomography (PET). Accordingly, mannan has been transformed into (18)F-fluoromannan with (18)F-bicyclo[6.1.0]nonyne. In mouse aorta, the binding of [(18)F]fluoromannan to the atherosclerotic lesions was clearly visualized and was significantly higher compared to blocking assays (P < 0.001) or healthy mouse aorta (P < 0.001). In healthy rats the [(18)F]fluoromannan radioactivity accumulated largely in the macrophage-rich organs such as liver, spleen, and bone marrow and the excess excreted in urine. Furthermore, the corresponding (19)F-labeled mannan has been used to induce psoriasis and psoriatic arthritis in mice, which indicates that the biological function of mannan is preserved after the chemical modifications.
最近，已证明来自酿酒酵母的甘露聚糖能够在小鼠中诱发银屑病和银屑病关节炎，且其表型与相应的人类疾病相似。为了研究其病理过程，我们着手用氟 - 18（¹⁸F）标记甘露聚糖，并通过正电子发射断层扫描（PET）在体外和体内研究¹⁸F标记的甘露聚糖。相应地，甘露聚糖已通过¹⁸F - 双环[6.1.0]壬炔转化为¹⁸F - 氟甘露聚糖。在小鼠主动脉中，[¹⁸F]氟甘露聚糖与动脉粥样硬化病变的结合清晰可见，与阻断试验（P < 0.001）或健康小鼠主动脉（P < 0.001）相比显著更高。在健康大鼠中，[¹⁸F]氟甘露聚糖放射性主要积聚在富含巨噬细胞的器官如肝脏、脾脏和骨髓中，并通过尿液排出多余部分。此外，相应的¹⁹F标记的甘露聚糖已被用于在小鼠中诱发银屑病和银屑病关节炎，这表明化学修饰后甘露聚糖的生物学功能得以保留。
