title: 700-nm Zwitterionic Near-Infrared Fluorophores for Dual-Channel Image-Guided Surgery.
abstract: OBJECTIVE
  The purpose of this study was to develop a family of 700-nm zwitterionic pentamethine indocyanine near-infrared fluorophores that would permit dual-channel image-guided surgery.
  
  
  METHODS
  Three complementary synthetic schemes were used to produce novel zwitterionic chemical structures. Physicochemical, optical, biodistribution, and clearance properties were compared to Cy5.5, a conventional pentamethine indocyanine now used for biomedical imaging.
  
  
  RESULTS
  ZW700-1a, ZW700-1b, and ZW700-1c were synthesized, purified, and analyzed extensively in vitro and in vivo. All molecules had extinction coefficients ≥199,000 M(-1) cm(-1), emission ≥660 nm, and stability ≥99 % after 24 h in warm serum. In mice, rats, and pigs, ≥80 % of the injected dose was completely eliminated from the body via renal clearance within 4 h. Either alone or conjugated to a tumor targeting ligand, ZW700-1a permitted dual-channel, high SBR, and simultaneous imaging with 800-nm NIR fluorophores using the FLARE® imaging system.
  
  
  CONCLUSIONS
  Novel 700-nm zwitterionic NIR fluorophores enable dual-NIR image-guided surgery.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Room SL-436A, Boston, MA, 02215, USA.
authors.forename: Hoon
authors.initials: H
authors.lastname: Hyun
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Ave. SE, Atlanta, GA, 30303, USA. mhenary1@gsu.edu.
authors.forename: Maged
authors.initials: M
authors.lastname: Henary
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Ave. SE, Atlanta, GA, 30303, USA.
authors.forename: Tielong
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Ave. SE, Atlanta, GA, 30303, USA.
authors.forename: Lakshminarayana
authors.initials: L
authors.lastname: Narayana
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Ave. SE, Atlanta, GA, 30303, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Owens
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Room SL-436A, Boston, MA, 02215, USA.
authors.forename: Jeong Heon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Room SL-436A, Boston, MA, 02215, USA.
authors.forename: GwangLi
authors.initials: G
authors.lastname: Park
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Room SL-436A, Boston, MA, 02215, USA.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Wada
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Room SL-436A, Boston, MA, 02215, USA.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Ashitate
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Room SL-436A, Boston, MA, 02215, USA.|Curadel, LLC, 377 Plantation Street, Worcester, MA, 01605, USA.
authors.forename: John V
authors.initials: JV
authors.lastname: Frangioni
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Room SL-436A, Boston, MA, 02215, USA. hchoi@bidmc.harvard.edu.|Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, 609-735, South Korea. hchoi@bidmc.harvard.edu.
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
mesh_terms: D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007430:Intraoperative Care; D008819:Mice, Nude; D061848:Optical Imaging / Q000379:methods*; D055620:Optical Phenomena; D019265:Spectroscopy, Near-Infrared; D025321:Surgery, Computer-Assisted / Q000379:methods*; D034421:Sus scrofa; D014018:Tissue Distribution
chemical_list: D005456:Fluorescent Dyes
keywords: Image-guided surgery; Near-infrared fluorescence; Optical imaging; Signal-to-background ratio