Theranostics 2014; 4(8):823-833. doi:10.7150/thno.8696

Research Paper

Prototype Nerve-Specific Near-Infrared Fluorophores

Min Ho Park1,2*, Hoon Hyun1*, Yoshitomo Ashitate1,3, Hideyuki Wada1,3, GwangLi Park1, Jeong Heon Lee1, Costyl Njiojob4, Maged Henary4, John V. Frangioni1,5,6, Hak Soo Choi1,7✉

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.
3. Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
4. Department of Chemistry, Georgia State University, Atlanta, GA 30303.
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.
7. Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735, South Korea.
*These authors contributed equally to this work.

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.

Keywords: Real-time intraoperative identification, nerve targeting, recurrent laryngeal nerve, contrast agents, targeted agents, near-infrared imaging.

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How to cite this article:
Park MH, Hyun H, Ashitate Y, Wada H, Park G, Lee JH, Njiojob C, Henary M, Frangioni JV, Choi HS. Prototype Nerve-Specific Near-Infrared Fluorophores. Theranostics 2014; 4(8):823-833. doi:10.7150/thno.8696. Available from http://www.thno.org/v04p0823.htm