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Targeting the alpha(v)beta 3 Integrin for Small-Animal PET/CT of Osteolytic Bone Metastases
Journal article   Open access   Peer reviewed

Targeting the alpha(v)beta 3 Integrin for Small-Animal PET/CT of Osteolytic Bone Metastases

Thaddeus J. Wadas, Hongju Deng, Jennifer E. Sprague, Alexander Zheleznyak, Katherine N. Weilbaecher and Carolyn J. Anderson
The Journal of nuclear medicine (1978), Vol.50(11), pp.1873-1880
11/01/2009
DOI: 10.2967/jnumed.109.067140
PMCID: PMC2836828
PMID: 19875645
url
https://doi.org/10.2967/jnumed.109.067140View
Published (Version of record) Open Access

Abstract

This article describes the evaluation of the radiopharmaceutical Cu-64-CB-TE2A-c(RGDyK) (Cu-64-RGD) as an imaging agent for osteolytic bone metastases and their associated inflammation by targeting of the alpha v beta 3 integrin on osteoclasts and the proinflammatory cells involved at the bone metastatic site. Methods: The Cu-64-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 Cu-64-RGD to determine whether this radiopharmaceutical was sensitive enough to detect a response to the bisphosphonate therapy. Results: Biodistribution studies using Cu-64-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 wildtype (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 alpha v beta 3-expressing cells. Small-animal PET/CT with Cu-64-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 Cu-64-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.
 Life Sciences & Biomedicine Radiology, Nuclear Medicine & Medical Imaging Science & Technology

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