Near-infrared-labeled tetracycline derivative is an effective marker of bone deposition in mice

Joy L. Kovar, Xinshe Xu, Dan Draney, Andrea Cupp, Melanie A. Simpson, D. Michael Olive

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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 6 weeks 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.

Original languageEnglish (US)
Pages (from-to)167-173
Number of pages7
JournalAnalytical Biochemistry
Volume416
Issue number2
DOIs
StatePublished - Sep 15 2011

Keywords

  • Fluorescence microscopy
  • IRDye 800CW
  • Immunofluorescent assay
  • Mineralization
  • Molecular imaging
  • Near-infrared
  • Tetracycline derivative
  • Whole animal imaging

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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