RT Journal Article
SR Electronic
T1 Targeting the α<sub>v</sub>β<sub>3</sub> Integrin for Small-Animal PET/CT of Osteolytic Bone Metastases
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1873
OP 1880
DO 10.2967/jnumed.109.067140
VO 50
IS 11
A1 Thaddeus J. Wadas
A1 Hongju Deng
A1 Jennifer E. Sprague
A1 Alexander Zheleznyak
A1 Katherine N. Weilbaecher
A1 Carolyn J. Anderson
YR 2009
UL http://jnm.snmjournals.org/content/50/11/1873.abstract
AB 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 αvβ3 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 αvβ3-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.