title: Radiolabeled and near-infrared fluorescent fibrinogen derivatives create a system for the identification and repair of obscure gastrointestinal bleeding.
abstract: BACKGROUND
  Gastrointesintal hemorrhage is often difficult to localize. A test that does not depend on active bleeding might prove clinically useful. We tested 2 novel fibrinogen (FBG)-based contrast agents for their ability to localize gastrointestinal (GI) hemorrhage after bleeding stopped. 125I-FBG permits gamma ray-based preoperative or intraoperative scanning, and near-infrared (NIR) flourescent FBG (FBG800) permits real-time intraoperative visualization of active clot.
  
  
  METHODS
  Bovine FBG was radiolabeled with 125I or conjugated to the NIR fluorophore CW800. Sites of bleeding were created by gastrotomy, mucosal resection of the stomach, or laceration of a mesenteric vessel; then 1.7 mg/kg FBG800 or 15 microCi/kg 125I-FBG was injected intravenously into mice, rabbits, or pigs 30 minutes before or after injury. Sites of active clot were quantified by using gamma counting and were also imaged by using invisible NIR light intraoperatively, for up to 3 hours postinjection.
  
  
  RESULTS
  After an injection of either 125I-FBG or FBG800, sites of prior bleeding could be identified in the absence of active bleeding. Blood clearance was such that a signal-to-background ratio of 2.0 or greater could be achieved within 20 minutes after injection. A similarly labeled human serum albumin did not accumulate at any site, with an SBR of 1.0 or less.
  
  
  CONCLUSIONS
  Both radiolabeled (preoperative gamma scanning) and NIR fluorescent (intraoperative real-time imaging) FBG can be used in experimental situations to identify the location of prior bleeding in the absence of active bleeding. Taken together, these contrast agents create a system for the identification and control of obscure GI bleeding.
authors.affiliation: Division of Hematology/Oncology, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ohnishi
authors.forename: Evan S
authors.initials: ES
authors.lastname: Garfein
authors.forename: Seth J
authors.initials: SJ
authors.lastname: Karp
authors.forename: John V
authors.initials: JV
authors.lastname: Frangioni
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology; D005340:Fibrinogen / Q000502:physiology; D005456:Fluorescent Dyes; D006471:Gastrointestinal Hemorrhage / Q000175:diagnosis*; D007457:Iodine Radioisotopes; D051379:Mice; D009780:Occult Blood; D011817:Rabbits; D013050:Spectrometry, Fluorescence; D013552:Swine; D013927:Thrombosis / Q000175:diagnosis
chemical_list: D005456:Fluorescent Dyes; D007457:Iodine Radioisotopes; D005340:Fibrinogen