αv-整合素超声分子成像可视化评价基质胶血管新生

Visually assessment of matrigel angiogenesis with ultrasound molecular imaging using microbubbles targeted to endothelial αv-integrins

目的 探讨应用携带αv-整合素分子探针的分子成像可视化评价基质胶血管新生的可行性.方法 10只实验小鼠分别于腹部皮下注射添碱性成纤维细胞生长因子（FGF）-2的基质胶制备血管新生模型.于注射后第10 d所有小鼠经尾静脉随机先后（间隔30min）弹丸注射携抗小鼠αv-整合素单抗靶向微泡（MBα）、携同型抗体对照微泡（MBc）,并分别于注入后6 min行基质胶超声造影检查,测量基质胶的显影强度（video intensity,VI）.随后,所有小鼠均预先αMBcv-整合素单抗封闭10 min后再注入MBα和MBc行超声造影检查.最后进行基质胶组织学检查.结果 超声造影图像显示MBα组呈明显的超声显影,VI值高达（20.5±3.3）U,而MBc组仅见轻度的超声显影,其VI为（4.8±1.5）U,两者之间差异有统计学意义（P＜0.05）.预先单抗封闭αv-整合素后,MBα的VI值仅为封闭前的22.4%,两者之间差异有统计学意义（P＜0.05） 而MBα的VI值较封闭前无明显变化,两者之间差异无统计学意义（P＞0.05）.病理学检查显示基质胶中有丰富的新生血管形成,新生血管中有大量αv-整合素表达.结论 应用携带αv-整合素分子探针的超声分子成像可有效特异地评价基质胶血管新生.

Objective To explore the feasibility of visually assessment of angiogenesis in a murine model of subcutaneous matrigel plugs with ultrasound molecular imaging（UMI） using microbubbles（MB）targeted to endothelial αv-integrins. Methods Matrigel angiogenesis was created by subcutaneous implantation of FGF-2 enriched matrigel in 10 mice. On day 10, UMI of the matrigel was performed in all mice at 6 minutes after intravenous injection of either αv-integrin targeting microbubbles（MBα） or isotype control microbubbles（MBc） in random with 30 min interval,and the video intensity（Ⅵ） was measured. To further test the specificity of the signal coming from MBα,antibody against αv-integrin was injected 10 min before microbubbles injection. Following UMI,all matrigels were harvested for histological analysis. Results As expected,VI of the matrigel was significantly higher （ P 〈0.05） for MBα （20. 5 ± 3.3）U as compared with MBc （4. 8 ± 1.5）U. After blocking with antibody against αv-integrin,a great decrease was observed in the MBα group [VI （4.6 ± 1.2） U, P 〈0.05] while no significant difference was noted for MBc [VI （4. 9 ±1.5）U, P 〉 0.05 ]. Neovessels within matrigel was positive for αv-integrin. Conclusions UMI with microbubbles targeted to αv-integrins can be effective and specific in evaluating the angiogenesis in a murine model of subcutaneous matrigel plugs.