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• W2142098425 abstract "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 α_vβ₃ integrin on osteoclasts and the proinflammatory cells involved at the bone metastatic site. <b>Methods:</b> 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. <b>Results:</b> 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 (<i>P</i> = 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 (<i>P</i> = 0.003), suggesting that earlier bone metastases cause an increased recruitment of α_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 (<i>P</i> = 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. <b>Conclusion:</b> 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." @default.
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• W2142098425 date "2009-10-29" @default.
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• W2142098425 title "Targeting the α_vβ₃ Integrin for Small-Animal PET/CT of Osteolytic Bone Metastases" @default.
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• W2142098425 doi "https://doi.org/10.2967/jnumed.109.067140" @default.
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