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

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

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

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

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 alpha(v)beta3 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 (t(1/2), 12.7 h; beta+, 17.4%; E(beta+ max), 656 keV; beta-, 39%; E(beta- max), 573 keV). The in vitro affinity of Cu(II)-CB-TE2A-c(RGDyK) for alpha(v)beta3 and alpha(v)beta5 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 alpha(v)beta3 than for alpha(v)beta5. Osteoclasts were shown to specifically take up (64)Cu-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 alpha(v)beta3 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.

Noninvasive imaging of osteoclasts in parathyroid hormone-induced osteolysis using a 64Cu-labeled RGD peptide. Publishing Authors By Initials

JE Sprague,H Kitaura,W Zou,Y Ye,S Achilefu,KN Weilbaecher,SL Teitelbaum,CJ Anderson,

For similar proteins: blood proteins: vitronectin research abstracts see: proteins: blood proteins: vitronectin research

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

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of nuclear medicine : official publication

VOLUME: 48

Page Numbers: 311-8

Journal Abbreviation: J. Nucl. Med.

ISSN: 0161-5505

DAY: 3

MONTH: Feb

YEAR: 2007

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

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LANGUAGE: eng

NlmUniqueID: 217410

Noninvasive imaging of osteoclasts in parathyroid hormone-induced osteolysis using a 64Cu-labeled RGD peptide. Keywords Mesh Terms:

KEYWORDS: Vitronectin

MESH TERMS: diagnostic use

Chemical & Substance for Abstract: Noninvasive imaging of osteoclasts in parathyroid hormone-induced osteolysis using a 64Cu-labeled RGD peptide. Information

Substance Name: arginyl-glycyl-aspartic acid

Registry Number: 99896-85-2

Grant and Affiliation Information for Noninvasive imaging of osteoclasts in parathyroid hormone-induced osteolysis using a 64Cu-labeled RGD peptide.

AFFILIATION: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Country: United States

AGENCY: United States NCI

GRANT: R24 CA86307

ACRONYM: CA

MEDLINETA: J Nucl Med

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