Molecular Imaging and Biology

, Volume 14, Issue 4, pp 500–508

Integrin αvβ3 as a PET Imaging Biomarker for Osteoclast Number in Mouse Models of Negative and Positive Osteoclast Regulation

  • Alexander Zheleznyak
  • Thaddeus J. Wadas
  • Christopher D. Sherman
  • Jessica M. Wilson
  • Paul J. Kostenuik
  • Katherine N. Weilbaecher
  • Carolyn J. Anderson
Research Article

DOI: 10.1007/s11307-011-0512-4

Cite this article as:
Zheleznyak, A., Wadas, T.J., Sherman, C.D. et al. Mol Imaging Biol (2012) 14: 500. doi:10.1007/s11307-011-0512-4

Abstract

Purpose

The goal of this study was to determine the specificity of 64Cu-CB-TE2A-c(RGDyK) (64Cu-RGD) for osteoclast-related diseases, such as Paget's disease or rheumatoid arthritis.

Procedures

C57BL/6 mice were treated systemically with osteoprotegerin (OPG) for 15 days or RANKL for 11 days to suppress and stimulate osteoclastogenesis, respectively. The mice were then imaged by positron emission tomography/computed tomography using 64Cu-RGD, followed by determination of serum TRAP5b and bone histology. Standard uptake values were determined to quantify 64Cu-RGD in bones and other tissues.

Results

Mice treated with OPG showed decreased bone uptake of 64Cu-RGD at 1, 2, and 24 h post-injection of the tracer (p < 0.01 for all time points) compared to vehicle controls, which correlated with a post-treatment decrease in serum TRAP5b. In contrast, mice treated with RANKL showed significantly increased bone uptake at 2 h post-injection of 64Cu-RGD (p < 0.05) compared to the vehicle control group, corresponding to increased serum TRAP5b and OC numbers as determined by bone histology.

Conclusions

These data demonstrate that 64Cu-RGD localizes to areas in bone with increased osteoclast numbers and support the use of 64Cu-RGD as an imaging biomarker for osteoclast number that could be used to monitor osteoclast-related pathologies and their treatments.

Key words

PET imaging Copper-64 Osteoclast regulation Integrin 

Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2011

Authors and Affiliations

  • Alexander Zheleznyak
    • 1
  • Thaddeus J. Wadas
    • 1
    • 6
  • Christopher D. Sherman
    • 1
  • Jessica M. Wilson
    • 1
  • Paul J. Kostenuik
    • 5
  • Katherine N. Weilbaecher
    • 2
  • Carolyn J. Anderson
    • 1
    • 3
    • 4
    • 7
  1. 1.Mallinckrodt Institute of RadiologyWashington University School of MedicineSt. LouisUSA
  2. 2.Department of MedicineWashington University School of MedicineSt. LouisUSA
  3. 3.Department of Biochemistry & Molecular BiophysicsWashington University School of MedicineSt. LouisUSA
  4. 4.Department of ChemistryWashington UniversitySt. LouisUSA
  5. 5.Department of Metabolic DisordersAmgen, Inc.Thousand OaksUSA
  6. 6.Department of Cancer BiologyWake Forest UniversityWinston-SalemUSA
  7. 7.Department of RadiologyUniversity of PittsburghPittsburghUSA

Personalised recommendations