title: Intraoperative Near-Infrared Fluorescence Imaging of Thymus in Preclinical Models.
abstract: BACKGROUND
  There are currently no thymus-specific contrast agents for biomedical imaging. Thus, finding ectopic thymic tissue during certain operations is extremely difficult. The purpose of the present study was to determine if near-infrared (NIR) fluorescence imaging could provide high sensitivity, real-time identification of thymic tissue during the operation.
  
  
  METHODS
  After initial in vivo screening of a 315-compound NIR fluorophore library for thymic uptake, methylene blue and five different 700-nm emitting candidate molecules were injected into CD-1 mice for quantitation of the signal-to-background ratio as a function of kinetics and dosing. Results were confirmed in 35-kg Yorkshire pigs. Dual-channel NIR imaging was also performed using a variety of 800-nm emitting NIR fluorophores targeted to various tissues in the mediastinum and neck.
  
  
  RESULTS
  The compound Oxazine 170 demonstrated the highest signal-to-background ratio (≥3) for thymic tissue relative to mediastinal fat, heart, lung, muscle, thyroid gland, and parathyroid gland, with peak signal-to-background ratio occurring 4 h after 1 intravenous injection of a human equivalent dose of approximately 7 mg. Simultaneous dual-channel NIR imaging permitted unambiguous identification of the thymus from surrounding tissues, such as endocrine glands and lymph nodes.
  
  
  CONCLUSIONS
  In mouse and pig, NIR fluorescence imaging using Oxazine 170 permits high sensitivity, real-time identification of thymic tissue for surgical procedures requiring its resection or avoidance. The performance of Oxazine 170 for imaging human thymic tissue is currently not known.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Wada
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Hoon
authors.initials: H
authors.lastname: Hyun
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Homan
authors.initials: H
authors.lastname: Kang
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Julien
authors.initials: J
authors.lastname: Gravier
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, Georgia.
authors.forename: Maged
authors.initials: M
authors.lastname: Henary
authors.affiliation: Curadel, LLC, Marlborough, Massachusetts.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Bordo
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Curadel, LLC, Marlborough, Massachusetts; Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Electronic address: papers@curadel.com.
authors.forename: John V
authors.initials: JV
authors.lastname: Frangioni
mesh_terms: D000818:Animals; D003287:Contrast Media; D008751:Methylene Blue; D051379:Mice; D008815:Mice, Inbred Strains; D061848:Optical Imaging; D010078:Oxazines; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013552:Swine; D013950:Thymus Gland / Q000000981:diagnostic imaging*
chemical_list: D003287:Contrast Media; D010078:Oxazines; D008751:Methylene Blue