HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wadas, T. J. Articles by Anderson, C. J. PubMed PubMed Citation Articles by Wadas, T. J. Articles by Anderson, C. J.

Targeting the _vβ₃ Integrin for Small-Animal PET/CT of Osteolytic Bone Metastases

¹ Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri; ² Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; ³ Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri; ⁴ Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri; and ⁵ Department of Chemistry, Washington University, St. Louis, Missouri

Correspondence: For correspondence or reprints contact: Carolyn J. Anderson, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd., Campus Box 8225, St. Louis, MO 63110. E-mail: andersoncj{at}wustl.edu

This article describes the evaluation of the radiopharmaceutical ⁶⁴Cu-CB-TE2A-c(RGDyK) (⁶⁴Cu-RGD) as an imaging agent for osteolytic bone metastases and their associated inflammation by targeting of the _vβ₃ integrin on osteoclasts and the proinflammatory cells involved at the bone metastatic site. Methods: The ⁶⁴Cu-RGD radiotracer was evaluated in the transgenic mouse expressing Tax (Tax⁺), which spontaneously develops osteolytic tumors throughout the vertebrae and hind limbs, using biodistribution studies and small-animal PET/CT. Histologic analysis was also performed on Tax⁺ mouse tails, using hematoxylin and eosin and tartrate-resistant acid phosphatase to confirm the presence of osteolytic bone lesions and the presence of osteoclasts, respectively. Additionally, a proof-of-principle study was conducted with a small group of Tax⁺ animals presenting with osteolytic lesions. These animals were treated with the bisphosphonate zoledronic acid and imaged with ⁶⁴Cu-RGD to determine whether this radiopharmaceutical was sensitive enough to detect a response to the bisphosphonate therapy. Results: Biodistribution studies using ⁶⁴Cu-RGD demonstrated that Tax⁺ mice between the ages of 6 and 12 mo had a greater accumulation of activity in their tail vertebrae than did the wild-type (WT) cohort (P = 0.013). Additionally, Tax⁺ mice between the ages of 6 and 12 mo had significantly more tracer activity associated with their tail vertebrae than did Tax⁺ mice older than 12 mo (P = 0.003), suggesting that earlier bone metastases cause an increased recruitment of _vβ₃-expressing cells. Small-animal PET/CT with ⁶⁴Cu-RGD was conducted on Tax⁺ and WT mice. On the basis of standardized uptake value analysis, Tax⁺ mice had approximately 2-fold more tail-associated activity than did WT animals (P = 0.0157). Additionally, decreases in uptake were observed in the tails of Tax⁺ mice after treatment with the osteoclast inhibitor zoledronic acid, and histologic analysis of Tax⁺ mouse-tail vertebrae revealed the presence of Tax⁺ tumor cells, osteoclasts, and proinflammatory cells within the bone microenvironment. Conclusion: Together, these data suggest that ⁶⁴Cu-RGD has the potential to effectively image osteolytic bone metastases and monitor the physiologic changes in the bone metastatic microenvironment after osteoclast-inhibiting bisphosphonate therapy.

Key Words: bone • metastasis • integrin • PET • bisphosphonate

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.

Related articles in JNM:

This Month in JNM

JNM 2009 50: 11A-12A. [Full Text]