Ohnishi S, Vanderheyden J-L, Tanaka E, Patel B, De Grand A M, Laurence R G, Yamashita K, Frangioni J V
Division of Hematology/Oncology, Beth Israek Deaconess Medical Center, Boston, Massachusetts, USA.
Am J Transplant. 2006 Oct;6(10):2321-31. doi: 10.1111/j.1600-6143.2006.01469.x. Epub 2006 Jul 25.
The intraoperative detection of cell injury and cell death is fundamental to human surgeries such as organ transplantation and resection. Because of low autofluorescence background and relatively high tissue penetration, invisible light in the 800 nm region provides sensitive detection of disease pathology without changing the appearance of the surgical field. In order to provide surgeons with real-time intraoperative detection of cell injury and death after ischemia/reperfusion (I/R), we have developed a bioactive derivative of human annexin V (annexin800), which fluoresces at 800 nm. Total fluorescence yield, as a function of bioactivity, was optimized in vitro, and final performance was assessed in vivo. In liver, intestine and heart animal models of I/R, an optimal signal to background ratio was obtained 30 min after intravenous injection of annexin800, and histology confirmed concordance between planar reflectance images and actual deep tissue injury. In summary, annexin800 permits sensitive, real-time detection of cell injury and cell death after I/R in the intraoperative setting, and can be used during a variety of surgeries for rapid assessment of tissue and organ status.
术中检测细胞损伤和细胞死亡对于器官移植和切除等人类手术至关重要。由于自荧光背景低且组织穿透性相对较高,800nm区域的不可见光可在不改变手术视野外观的情况下灵敏地检测疾病病理。为了为外科医生提供缺血/再灌注(I/R)后细胞损伤和死亡的术中实时检测,我们开发了一种人膜联蛋白V的生物活性衍生物(膜联蛋白800),它在800nm处发出荧光。作为生物活性函数的总荧光产量在体外进行了优化,并在体内评估了最终性能。在I/R的肝、肠和心脏动物模型中,静脉注射膜联蛋白800后30分钟获得了最佳的信号与背景比率,并且组织学证实了平面反射图像与实际深部组织损伤之间的一致性。总之,膜联蛋白800能够在术中灵敏地实时检测I/R后的细胞损伤和细胞死亡,并且可用于各种手术中以快速评估组织和器官状态。