title: Charge and hydrophobicity effects of NIR fluorophores on bone-specific imaging.
abstract: Recent advances in near-infrared (NIR) fluorescence imaging enabled real-time intraoperative detection of bone metastases, bone growth, and tissue microcalcification. Pamidronate (PAM) has been widely used for this purpose because of its high binding affinity toward bone and remarkable therapeutic effects. Herein we describe the development of a series of PAM-conjugated NIR fluorophores that varied in net charges and hydrophobicity, and compared their bone targeting efficiency, biodistribution, and blood clearance. Since the targeting moiety, PAM, is highly negatively charged but small, the overall in vivo bone targeting and biodistribution were mediated by the physicochemical properties of conjugated fluorophores.
authors.affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215; ; 2. Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, China, 110016;
authors.forename: Kai
authors.initials: K
authors.lastname: Bao
authors.affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215; ; 3. Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Khaled A
authors.initials: KA
authors.lastname: Nasr
authors.affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;
authors.forename: Hoon
authors.initials: H
authors.lastname: Hyun
authors.affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;
authors.forename: Jeong Heon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;
authors.forename: Julien
authors.initials: J
authors.lastname: Gravier
authors.affiliation: 4. Department of Biomedical Engineering, OHSU Center for Spatial Systems Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201.
authors.forename: Summer L
authors.initials: SL
authors.lastname: Gibbs
authors.affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000473:pathology*; D002114:Calcinosis / Q000473:pathology; D004164:Diphosphonates / Q000737:chemistry; D005260:Female; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D000077268:Pamidronate; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D055672:Static Electricity; D014018:Tissue Distribution
chemical_list: D004164:Diphosphonates; D005456:Fluorescent Dyes; D000077268:Pamidronate
keywords: Bone targeting; Charge and hydrophobicity; Microcalcification; Near-infrared fluorophores; Zwitterionic fluorophores.
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