title: Integrin α(v)β₃ as a PET imaging biomarker for osteoclast number in mouse models of negative and positive osteoclast regulation.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zheleznyak
authors.forename: Thaddeus J
authors.initials: TJ
authors.lastname: Wadas
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Sherman
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Wilson
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kostenuik
authors.forename: Katherine N
authors.initials: KN
authors.lastname: Weilbaecher
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Anderson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D064847:Multimodal Imaging; D009928:Organ Specificity / Q000187:drug effects; D009942:Organometallic Compounds; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D053244:Osteoprotegerin / Q000008:administration & dosage / Q000494:pharmacology; D049268:Positron-Emission Tomography / Q000379:methods*; D053245:RANK Ligand / Q000008:administration & dosage / Q000494:pharmacology; D015203:Reproducibility of Results; D014057:Tomography, X-Ray Computed
chemical_list: C483895:(4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane)copper(II); D015415:Biomarkers; D039302:Integrin alphaVbeta3; D009942:Organometallic Compounds; D053244:Osteoprotegerin; D053245:RANK Ligand