Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Dr, Room H1307; Stanford, CA 94305-5621, USA.
Radiology. 2013 Jun;267(3):818-29. doi: 10.1148/radiol.13122509. Epub 2013 Jan 31.
To develop and test a molecular imaging approach that uses ultrasonography (US) and a clinically translatable dual-targeted (P- and E-selectin) contrast agent (MBSelectin) in the quantification of inflammation at the molecular level and to quantitatively correlate selectin-targeted US with fluorodeoxyglucose (FDG) combined positron emission tomography (PET) and computed tomography (CT) in terms of visualization and quantification of different levels of inflammation in a murine acute colitis model.
Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care at Stanford University. MBSelectin was developed by covalently binding an analog of the naturally occurring binding ligand P-selectin glycoprotein ligand 1 fused to a human fragment crystallizable(or Fc) domain onto the lipid shell of perfluorobutane and nitrogen-containing MBs. Binding specificity of MBSelectin was assessed in vitro with a flow chamber assay and in vivo with a chemically induced acute colitis murine model. US signal was quantitatively correlated with FDG uptake at PET/CT and histologic grade. Statistical analysis was performed with the Student t test, analysis of variance, and Pearson correlation analysis.
MBSelectin showed strong attachment to both human and mouse P- and E-selectin compared with MBControl in vitro (P ≤ .002). In vivo, US signal was significantly increased (P < .001) in mice with acute colitis (173.8 arbitrary units [au] ± 134.8 [standard deviation]) compared with control mice (5.0 au ± 4.5). US imaging signal strongly correlated with FDG uptake on PET/CT images (ρ = 0.89, P < .001). Ex vivo analysis enabled confirmation of inflammation in mice with acute colitis and high expression levels of P- and E-selectin in mucosal capillaries (P = .014).
US with MBSelectin specifically enables detection and quantification of inflammation in a murine acute colitis model, leveraging the natural pathway of leukocyte recruitment in inflammatory tissue. US imaging with MBSelectin correlates well with FDG uptake at PET/CT imaging.
开发和测试一种分子成像方法，该方法使用超声（US）和一种临床可转化的双重靶向（P-和 E-选择素）对比剂（MBSelectin），在分子水平定量炎症，并定量相关选择素靶向 US 与氟脱氧葡萄糖（FDG）结合正电子发射断层扫描（PET）和计算机断层扫描（CT）在可视化和定量不同水平的炎症在小鼠急性结肠炎模型中。
动物研究得到斯坦福大学机构动物护理管理小组的批准。MBSelectin 通过将天然结合配体 P-选择素糖蛋白配体 1 的类似物与人类片段结晶（或 Fc）结构域共价结合到全氟丁烷和含氮 MB 的脂质壳上来制备。在体外通过流动室测定和体内通过化学诱导的急性结肠炎小鼠模型评估 MBSelectin 的结合特异性。US 信号与 FDG 摄取在 PET/CT 和组织学分级进行定量相关。采用学生 t 检验、方差分析和皮尔逊相关分析进行统计学分析。
MBSelectin 与 MBControl 相比，在体外对人源和鼠源 P-和 E-选择素的附着能力较强（P ≤.002）。在体内，与对照小鼠（5.0 au ± 4.5）相比，急性结肠炎小鼠（173.8 个任意单位 [au] ± 134.8 [标准差]）的 US 信号显著增加（P <.001）。US 成像信号与 PET/CT 图像上的 FDG 摄取强烈相关（ρ = 0.89，P <.001）。离体分析证实了急性结肠炎小鼠的炎症和黏膜毛细血管中 P-和 E-选择素的高表达水平（P =.014）。
MBSelectin 的 US 特异性地检测和定量小鼠急性结肠炎模型中的炎症，利用白细胞在炎症组织中募集的天然途径。MBSelectin 的 US 成像与 FDG 在 PET/CT 成像中的摄取具有很好的相关性。
