Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging


H. Hyun, M. H. Park, E. A. Owens, H. Wada, M. Henary, H. J. Handgraaf, A. L. Vahrmeijer, J. V. Frangioni, and H. S. Choi. 2015. “Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging.” Nat Med, 21, Pp. 192-7.


The typical method for creating targeted contrast agents requires covalent conjugation of separate targeting and fluorophore domains. In this study, we demonstrate that it is possible to create near-infrared (NIR) fluorophores with different tissue specificities driven by their inherent chemical structures. Thus, a single compact molecule performs both targeting and imaging. We use this strategy to solve a major problem in head and neck surgery: the identification and preservation of parathyroid and thyroid glands. We synthesized 700-nm and 800-nm halogenated fluorophores that show high uptake into these glands after a single intravenous (IV) injection of 0.06 mg kg(-1) in a pig. By using a dual-channel NIR imaging system, we observed-in real time and with high sensitivity-the unambiguous distinction of parathyroid and thyroid glands simultaneously in the context of blood and surrounding soft tissue. This novel technology lays a foundation for performing head and neck surgery with increased precision and efficiency along with potentially lower morbidity, and it provides a general strategy for developing targeted NIR fluorophores.


Hyun, HoonPark, Min HoOwens, Eric AWada, HideyukiHenary, MagedHandgraaf, Henricus J MVahrmeijer, Alexander LFrangioni, John VChoi, Hak SooengR01-EB-010022/EB/NIBIB NIH HHS/R01-EB-011523/EB/NIBIB NIH HHS/R01-CA-115296/CA/NCI NIH HHS/R01 EB010022/EB/NIBIB NIH HHS/R01 EB011523/EB/NIBIB NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tNat Med. 2015 Feb;21(2):192-7. doi: 10.1038/nm.3728. Epub 2015 Jan 5.