title: Pancreas-targeted NIR fluorophores for dual-channel image-guided abdominal surgery.
abstract: OBJECTIVE
  Pancreas-related complications are some of the most serious ones in abdominal surgery. The goal of this study was to develop and validate novel near-infrared (NIR) fluorophores that would enable real-time pancreas imaging to avoid the intraoperative pancreatic injury.
  
  
  METHODS
  After initial screening of a large NIR fluorophore library, the performance of 3 selected pancreas-targeted 700 nm NIR fluorophores, T700-H, T700-F, and MB, were quantified in mice, rats, and pigs. Dose ranging using 25 and 100 nmol, and 2.5 µmol of T700-F, and its imaging kinetics over a 4 h period were tested in each species. Three different 800 nm NIR fluorophores were employed for dual-channel FLARE™ imaging in pigs: 2 μmol of ZW800-1 for vessels and kidney, 1 μmol of ZW800-3C for lymph nodes, and 2 μmol of ESNF31 for adrenal glands.
  
  
  RESULTS
  T700-F demonstrated the highest signal to background ratio (SBR), with peak SBR at 4 h postinjection in mice. In pigs, T700-F produced an SBR≥2 against muscle, spleen, and lymph nodes for up to 8 h after a single intravenous injection. The combination of T700-F with each 800 nm NIR fluorophore provided simultaneous dual-channel intraoperative imaging of pancreas with surrounding organs in real time.
  
  
  CONCLUSIONS
  Pancreas-targeted NIR fluorophores combined with the FLARE dual-channel imaging system enable the real-time intraoperative pancreas imaging which helps surgeons perform safer and more curative abdominal surgeries.
authors.affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215. ; 2. Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Wada
authors.affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
authors.forename: Hoon
authors.initials: H
authors.lastname: Hyun
authors.affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215. ; 3. Division of Plastic and Reconstructive Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215.
authors.forename: Christina
authors.initials: C
authors.lastname: Vargas
authors.affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215. ; 4. INSERM, CRI, U823, Institut Albert Bonniot, 38042 Grenoble, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Gravier
authors.affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
authors.forename: GwangLi
authors.initials: G
authors.lastname: Park
authors.affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Gioux
authors.affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215. ; 5. Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215. ; 6. Curadel, LLC, 377 Plantation Street, Worcester, MA 01605.
authors.forename: John V
authors.initials: JV
authors.lastname: Frangioni
authors.affiliation: 7. Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303.
authors.forename: Maged
authors.initials: M
authors.lastname: Henary
authors.affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215. ; 8. Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735, South Korea.
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D005456:Fluorescent Dyes / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D051379:Mice; D061848:Optical Imaging / Q000379:methods*; D010179:Pancreas / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013194:Staining and Labeling / Q000379:methods*; D025321:Surgery, Computer-Assisted / Q000379:methods*; D013552:Swine; D013997:Time Factors
chemical_list: D005456:Fluorescent Dyes
keywords: Image-guided surgery; Intraoperative pancreatic injury; Near-Infrared fluorescence.; Pancreas-related complications; Postoperative pancreatic fistula