Phosphonated Near‐Infrared Fluorophores for Biomedical Imaging of Bone |
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| Authors: | Dr. Hoon Hyun Dr. Hideyuki Wada Dr. Kai Bao Dr. Julien Gravier Dr. Yogesh Yadav Dr. Matt Laramie Dr. Maged Henary Dr. John V. Frangioni Dr. Hak Soo Choi |
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| Affiliation: | 1. Division of Hematology/Oncology, Department of Medicine and Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, SL436A, Boston, MA 02215 (USA);2. Department of Chemistry, Georgia State University, Atlanta, GA 30303 (USA);3. Curadel, LLC, 377 Plantation Street, Worcester, MA 01605 (USA);4. Department of Cogno‐Mechatronics Engineering, Pusan National University, Busan 609‐735 (South Korea) |
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| Abstract: | The conventional method for creating targeted contrast agents is to conjugate separate targeting and fluorophore domains. A new strategy is based on the incorporation of targeting moieties into the non‐delocalized structure of pentamethine and heptamethine indocyanines. Using the known affinity of phosphonates for bone minerals in a model system, two families of bifunctional molecules that target bone without requiring a traditional bisphosphonate are synthesized. With peak fluorescence emissions at approximately 700 or 800 nm, these molecules can be used for fluorescence‐assisted resection and exploration (FLARE) dual‐channel imaging. Longitudinal FLARE studies in mice demonstrate that phosphonated near‐infrared fluorophores remain stable in bone for over five weeks, and histological analysis confirms their incorporation into the bone matrix. Taken together, a new strategy for creating ultra‐compact, targeted near‐infrared fluorophores for various bioimaging applications is described. |
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| Keywords: | fluorophores imaging agents medicinal chemistry near‐infrared fluorescence |
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