Research Article

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 ZheleznyakAffiliated withMallinckrodt Institute of Radiology, Washington University School of Medicine
  • , Thaddeus J. WadasAffiliated withMallinckrodt Institute of Radiology, Washington University School of MedicineDepartment of Cancer Biology, Wake Forest University
  • , Christopher D. ShermanAffiliated withMallinckrodt Institute of Radiology, Washington University School of Medicine
  • , Jessica M. WilsonAffiliated withMallinckrodt Institute of Radiology, Washington University School of Medicine
  • , Paul J. KostenuikAffiliated withDepartment of Metabolic Disorders, Amgen, Inc.
  • , Katherine N. WeilbaecherAffiliated withDepartment of Medicine, Washington University School of Medicine
  • , Carolyn J. AndersonAffiliated withMallinckrodt Institute of Radiology, Washington University School of MedicineDepartment of Biochemistry & Molecular Biophysics, Washington University School of MedicineDepartment of Chemistry, Washington UniversityDepartment of Radiology, University of Pittsburgh Email author 

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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