Noninvasive imaging of osteoclasts in parathyroid hormone-induced osteolysis using a 64Cu-labeled RGD peptide

Jennifer E. Sprague, Hideki Kitaura, Wei Zou, Yunpeng Ye, Samuel Achilefu, Katherine N. Weilbaecher, Steven L. Teitelbaum, Carolyn J. Anderson

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59 Citations (Scopus)


Bone diseases are often a result of increased numbers of osteoclasts, or bone-resorbing cells. Bone metastases are a significant cause of morbidity in many types of cancer. An imaging agent targeting osteoclasts, which are upregulated in osteolytic lesions, may facilitate earlier follow-up in patients with osteolytic or mixed bone metastases. Osteoclasts express high levels of αvβ3 integrin, to which peptides containing the Arg-Gly-Asp (RGD) sequence are known to bind. We proposed that radiolabeled RGD peptides could be used to detect osteoclasts in lytic bone lesions. Methods: The cross-bridged macrocyclic chelator 4,11-bis(carboxymethyl)-1,4,8,11- tetraazabicyclo[6.6.2]hexadecane (CB-TE2A) was conjugated to c(RGDyK) for radiolabeling with 64Cu (t1/2, 12.7 h; β+, 17.4%; Eβ+max, 656 keV; β-, 39%; E β2max, 573 keV). The in vitro affinity of Cu(II)-CB-TE2A- c(RGDyK) for αvβ3 and αvβ 5 was evaluated in a heterologous competitive binding assay. Ex vivo uptake was examined in osteoclasts prepared from bone marrow macrophages. As a proof of principle, biodistribution and imaging studies were performed on parathyroid hormone (PTH)-induced osteolysis in the calvarium. Results: Cu-CB-TE2A-c(RGDyK) was shown to have a 30-fold higher affinity for αvβ3 than for αvβ 5. Osteoclasts were shown to specifically take up 64Cu-CB-TE2A-c(RGDyK). However, bone marrow macrophages showed only nonspecific uptake. PTH treatment increased calvarial uptake of 64Cu-CB-TE2A-c(RGDyK), compared with uptake in mice receiving a sham treatment. In addition, calvarial uptake correlated linearly with the number of osteoclasts on the bone surface. Conclusion: These results suggest that 64Cu-CB-TE2A-c(RGDyK) selectively binds αvβ 3 on osteoclasts and may potentially be used to identify increased numbers of osteoclasts in osteolytic bone diseases such as osteolytic bone metastasis and inflammatory osteolysis.

Original languageEnglish
Pages (from-to)311-318
Number of pages8
JournalJournal of Nuclear Medicine
Issue number2
Publication statusPublished - 2007 Feb 1


  • Bone
  • Copper-64
  • Integrin
  • Osteoclast
  • PET/CT
  • Radiopharmaceuticals


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