title: Near-infrared-labeled tetracycline derivative is an effective marker of bone deposition in mice.
abstract: Bone-specific compounds have been used effectively for the detection of bone mineralization, growth, and morphological changes. These agents typically contain iminodiacetic acid groups that can form complexes with apatite and fluoresce in the visible spectrum. We exploited a subset of these chemical chelators to produce a near-infrared (NIR) optical bone marker for preclinical animal imaging. By conjugating target compounds to IRDye 800CW, we extended the effective fluorescence signal detection to the NIR region without affecting the compound's ability to function as a marker of the mineralization process. Calcein and a tetracycline derivative (BoneTag agent [BT]) bound specifically to differentiated mineralized osteoblast cultures, with the latter exhibiting 6-fold higher signal intensities. Subsequent in vivo testing demonstrated effective skeletal labeling with IRDye 800CW BT. We were able to identify a changing mineralization front in bone sections from (i) normal growing mice injected with IRDye 800CW BT 6weeks prior to the administration of IRDye 680 BT and (ii) an osteoporosis mouse model comparing cortical bone in sham-treated and ovariectomized mice. These results provide evidence that the NIR-labeled BT is effective as a general marker of skeletal features and an indicator of the bone mineralization and remodeling processes.
authors.affiliation: Translational Research, LI-COR Biosciences, Lincoln, NE 68504, USA. joy.kovar@licor.com
authors.forename: Joy L
authors.initials: JL
authors.lastname: Kovar
authors.forename: Xinshe
authors.initials: X
authors.lastname: Xu
authors.forename: Dan
authors.initials: D
authors.lastname: Draney
authors.forename: Andrea
authors.initials: A
authors.lastname: Cupp
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Simpson
authors.forename: D Michael
authors.initials: DM
authors.lastname: Olive
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D016723:Bone Remodeling; D002113:Calcification, Physiologic; D002460:Cell Line; D004195:Disease Models, Animal; D005452:Fluoresceins / Q000737:chemistry; D007211:Indoles / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods; D010024:Osteoporosis / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013752:Tetracycline / Q000032:analysis* / Q000737:chemistry; D051598:Whole Body Imaging
chemical_list: D015415:Biomarkers; D005452:Fluoresceins; C427728:IRDye800; D007211:Indoles; D013752:Tetracycline; C007740:fluorexon