关节炎近红外荧光脱氧核糖衍生物的光学成像实验研究

Experimental Study on Optical Imaging of Arthritis Near- Infrared Fluorescent Deoxyglucose Derivatives

目的:研究近红外荧光分子探针,Cy5.5葡萄糖胺(Cy5.5-2DG),能否在活体水平上对小鼠诱导性关节炎(CIA)炎症进行显像。方法:对患有CIA的小鼠注射18F-脱氧葡萄糖(18F-FDG),1h后,进行Micro PET成像。在18F-FDG放射性衰变以后,通过尾静脉对小鼠注射Cy5.5-2DG。Cy5.5-2DG对关节炎组织的靶向性和保留性通过Xenogen IVIS 200光学成像仪进行评估和量化分析。患病小鼠体内的炎症组织通过18F-FDG-Micro PET扫描清晰可见,从该小鼠体内的Cy5.5-2DG的近红外荧光成像可以看出Cy5.5-2DG在关节组织的分布模式和18F-FDG极其相似;定量分析进一步表明关节炎组织在1 h后对18F-FDG的摄取量和Cy5.5-2DG在不同时刻的摄取量有很好的相关性(r2>0.65)。结果:18FFDG的摄取量和Cy5.5-2DG累积量之间良好的相关性,为进一步研究Cy5.5-2DG用于评估药物消炎治疗提供了依据。结论:NIRF葡萄糖衍生物Cy5.5-2DG可以检测小鼠手掌的关节炎组织,更重要的是Cy5.5-2DG在关节炎组织中的累积程度与18F-FDG摄取量有很大的正相关。

Objective： To investigate whether a Near- infrared fluorescence（ NIRF） probe,Cy5. 5- D- glucosamine（ Cy5. 5- 2DG）,can image arthritis in collagen- induced arthritic（ CIA） mice. Methods： The presence of arthritis was verified by both visual examination and micro- computed tomography（ Micro CT） imaging.CIA mice were imaged by a micro- positron emission tomography（ Micro PET） scanner 1- h after intravenous injection of 2- deoxy- 2-18 F fluoro- D- glucose（18F- FDG）. After radioactivity of18F- FDG decayed away,Cy5. 5- 2DG was injected into a lateral tail vein of the mice. Arthritic tissue targeting and retention of Cy5. 5-2DG in CIA mice were evaluated and quantified by an optical imaging system. Inflammatory tissues in CIA mice were clearly visualized by18F- FDG- Micro PET scan. NIRF imaging of Cy5. 5- 2DG in the same mice revealed that the pattern of localization of Cy5. 5- 2DG in the arthritic tissue was very similar to that of18F- FDG. Quantification analysis further showed that18F- FDG uptake in arthritic tissues at 1 h post- injection（ p. i.） and Cy5. 5-2DG uptakes at different time points p. i. were all well correlated（ r2 over 0. 65）. Results： The good correlation between the18F- FDG uptake and Cy5. 5- 2DG accumulation in the same arthritic tissues warrant further investigation of Cy5. 5- 2DG as an approach for assessment of anti- inflammatory treatments. Conclusion： Cy5. 5- 2DG can detect arthritic paws in living mice. More importantly,the extent of Cy5. 5- 2DG accumulation in arthritic tissues correlate very well with the18 FDG uptake. Therefore Cy5. 5- 2DG imaging may offer an approach for assessment of anti- inflammatory treatments and be used in imaging guided therapy.