title: Intraoperative detection of cell injury and cell death with an 800 nm near-infrared fluorescent annexin V derivative.
abstract: 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.
authors.affiliation: Division of Hematology/Oncology, Beth Israek Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ohnishi
authors.forename: J-L
authors.initials: JL
authors.lastname: Vanderheyden
authors.forename: E
authors.initials: E
authors.lastname: Tanaka
authors.forename: B
authors.initials: B
authors.lastname: Patel
authors.forename: A M
authors.initials: AM
authors.lastname: De Grand
authors.forename: R G
authors.initials: RG
authors.lastname: Laurence
authors.forename: K
authors.initials: K
authors.lastname: Yamashita
authors.forename: J V
authors.initials: JV
authors.lastname: Frangioni
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000493:pharmacokinetics; D016923:Cell Death; D004285:Dogs; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics; D016027:Heart Transplantation / Q000009:adverse effects; D007421:Intestine, Small / Q000098:blood supply / Q000473:pathology / Q000637:transplantation; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008856:Microscopy, Fluorescence; D016343:Monitoring, Intraoperative / Q000379:methods*; D011379:Prognosis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
chemical_list: D017304:Annexin A5; D004791:Enzyme Inhibitors