Hideyuki Wada1, Hoon Hyun2, Homan Kang3, Julien Gravier3, Maged Henary4, Mark W Bordo5, Hak Soo Choi3, John V Frangioni6. 1. 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. 2. 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. 3. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 4. Department of Chemistry, Georgia State University, Atlanta, Georgia. 5. Curadel, LLC, Marlborough, Massachusetts. 6. 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.
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.
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-1mice 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.
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