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.
Hyun, HoonWada, HideyukiBao, KaiGravier, JulienYadav, YogeshLaramie, MattHenary, MagedFrangioni, John VChoi, Hak SooGermanyInternational ed. in EnglishAngew Chem Int Ed Engl. 2014 Sep 26;53(40):10668-72. doi: 10.1002/anie.201404930. Epub 2014 Aug 19.