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Mol Imaging Biol. 2012 Aug;14(4):500-8. doi: 10.1007/s11307-011-0512-4.

Integrin α(v)β₃ as a PET imaging biomarker for osteoclast number in mouse models of negative and positive osteoclast regulation.

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  • 1Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.



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.


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.


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.


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.

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