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.
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We thank D. Burrington, Jr. for editing and E. Trabucchi for administrative assistance. This study was supported by the following grants from the National Institutes of Health: NCI BRP grant no. R01-CA-115296 (J.V.F.), NIBIB grant nos. R01-EB-010022 (J.V.F.) and R01-EB-011523 (H.S.C.), and a grant from the Dana Foundation in brain and immuno-imaging (H.S.C.). The contents of this paper are solely the responsibility of the authors and do not necessarily reflect the official views of the National Institutes of Health
J.V.F. is currently CEO of Curadel, LLC, which has licensed FLARE imaging systems and contrast agents from the Beth Israel Deaconess Medical Center.
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Hyun, H., Park, M., Owens, E. et al. Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging. Nat Med 21, 192–197 (2015) doi:10.1038/nm.3728
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