title: Phosphonated near-infrared fluorophores for biomedical imaging of bone.
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.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine and Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, SL436A, Boston, MA 02215 (USA).
authors.forename: Hoon
authors.initials: H
authors.lastname: Hyun
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Wada
authors.forename: Kai
authors.initials: K
authors.lastname: Bao
authors.forename: Julien
authors.initials: J
authors.lastname: Gravier
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Yadav
authors.forename: Matt
authors.initials: M
authors.lastname: Laramie
authors.forename: Maged
authors.initials: M
authors.lastname: Henary
authors.forename: John V
authors.initials: JV
authors.lastname: Frangioni
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000648:ultrastructure*; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000032:analysis*; D007267:Injections; D051379:Mice; D008819:Mice, Nude; D061848:Optical Imaging / Q000379:methods*; D063065:Organophosphonates / Q000008:administration & dosage / Q000032:analysis*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013552:Swine
chemical_list: D005456:Fluorescent Dyes; D063065:Organophosphonates
keywords: fluorophores; imaging agents; medicinal chemistry; near-infrared fluorescence