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 journalArticle

28 Citations (Scopus)

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

Fingerprint

Tetracycline
Physiologic Calcification
Bone
Infrared radiation
Derivatives
Bone and Bones
Apatites
Bone Remodeling
Bone Development
Chelating Agents
Osteoblasts
Osteoporosis
Fluorescence
Signal detection
Cell culture
Labeling
IRDye 800CW
Animals
Imaging techniques
Testing

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

Cite this

Near-infrared-labeled tetracycline derivative is an effective marker of bone deposition in mice. / Kovar, Joy L.; Xu, Xinshe; Draney, Dan; Cupp, Andrea; Simpson, Melanie A.; Michael Olive, D.

In: Analytical Biochemistry, Vol. 416, No. 2, 15.09.2011, p. 167-173.

Research output: Contribution to journalArticle

Kovar, Joy L. ; Xu, Xinshe ; Draney, Dan ; Cupp, Andrea ; Simpson, Melanie A. ; Michael Olive, D. / Near-infrared-labeled tetracycline derivative is an effective marker of bone deposition in mice. In: Analytical Biochemistry. 2011 ; Vol. 416, No. 2. pp. 167-173.
@article{4901ec468c10439d9ca9e4dd3872072c,
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 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.",
keywords = "Fluorescence microscopy, IRDye 800CW, Immunofluorescent assay, Mineralization, Molecular imaging, Near-infrared, Tetracycline derivative, Whole animal imaging",
author = "Kovar, {Joy L.} and Xinshe Xu and Dan Draney and Andrea Cupp and Simpson, {Melanie A.} and {Michael Olive}, D.",
year = "2011",
month = "9",
day = "15",
doi = "10.1016/j.ab.2011.05.011",
language = "English (US)",
volume = "416",
pages = "167--173",
journal = "Analytical Biochemistry",
issn = "0003-2697",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Near-infrared-labeled tetracycline derivative is an effective marker of bone deposition in mice

AU - Kovar, Joy L.

AU - Xu, Xinshe

AU - Draney, Dan

AU - Cupp, Andrea

AU - Simpson, Melanie A.

AU - Michael Olive, D.

PY - 2011/9/15

Y1 - 2011/9/15

N2 - 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.

AB - 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.

KW - Fluorescence microscopy

KW - IRDye 800CW

KW - Immunofluorescent assay

KW - Mineralization

KW - Molecular imaging

KW - Near-infrared

KW - Tetracycline derivative

KW - Whole animal imaging

UR - http://www.scopus.com/inward/record.url?scp=80155194389&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80155194389&partnerID=8YFLogxK

U2 - 10.1016/j.ab.2011.05.011

DO - 10.1016/j.ab.2011.05.011

M3 - Article

C2 - 21645491

AN - SCOPUS:80155194389

VL - 416

SP - 167

EP - 173

JO - Analytical Biochemistry

JF - Analytical Biochemistry

SN - 0003-2697

IS - 2

ER -