title: Prototype nerve-specific near-infrared fluorophores.
abstract: Nerve preservation is an important issue during most surgery because accidental transection or injury results in significant morbidity, including numbness, pain, weakness, or paralysis. Currently, nerves are still identified only by gross appearance and anatomical location during surgery, without intraoperative image guidance. Near-infrared (NIR) fluorescent light, in the wavelength range of 650-900 nm, has the potential to provide high-resolution, high-sensitivity, and real-time avoidance of nerve damage, but only if nerve-specific NIR fluorophores can be developed. In this study, we evaluated a series of Oxazine derivatives to highlight various peripheral nerve structures in small and large animals. Among the targeted fluorophores, Oxazine 4 has peak emission near into the NIR, which provided nerve-targeted signal in the brachial plexus and sciatic nerve for up to 12 h after a single intravenous injection. In addition, recurrent laryngeal nerves were successfully identified and highlighted in real time in swine, which could be preserved during the course of thyroid resection. Although optical properties of these agents are not yet optimal, chemical structure analysis provides a basis for improving these prototype nerve-specific NIR fluorophores even further.
authors: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215. ; 2. Department of Surgery, Chonnam National University Medical School, Gwangju 501-746, South Korea.
authors: Min Ho
authors: MH
authors: Park
authors: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
authors: Hoon
authors: H
authors: Hyun
authors: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215. ; 3. Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors: Yoshitomo
authors: Y
authors: Ashitate
authors: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215. ; 3. Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors: Hideyuki
authors: H
authors: Wada
authors: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
authors: GwangLi
authors: G
authors: Park
authors: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
authors: Jeong Heon
authors: JH
authors: Lee
authors: 4. Department of Chemistry, Georgia State University, Atlanta, GA 30303.
authors: Costyl
authors: C
authors: Njiojob
authors: 4. Department of Chemistry, Georgia State University, Atlanta, GA 30303.
authors: Maged
authors: M
authors: Henary
authors: 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: John V
authors: JV
authors: Frangioni
authors: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215. ; 7. Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735, South Korea.
authors: Hak Soo
authors: HS
authors: Choi
mesh_terms: D000818:Animals; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D007823:Laryngeal Nerves / Q000378:metabolism; D008297:Male; D009417:Nerve Tissue / Q000378:metabolism*; D055620:Optical Phenomena; D009928:Organ Specificity; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D034421:Sus scrofa
chemical_list: D005456:Fluorescent Dyes
keywords: Real-time intraoperative identification; contrast agents; near-infrared imaging.; nerve targeting; recurrent laryngeal nerve; targeted agents