Back to Search
Start Over
Targeting the alphavbeta3 integrin for small-animal PET/CT of osteolytic bone metastases
- Source :
- Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 50(11)
- Publication Year :
- 2009
-
Abstract
- This article describes the evaluation of the radiopharmaceutical (64)Cu-CB-TE2A-c(RGDyK) ((64)Cu-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.The (64)Cu-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 (64)Cu-RGD to determine whether this radiopharmaceutical was sensitive enough to detect a response to the bisphosphonate therapy.Biodistribution studies using (64)Cu-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 alpha(v)beta(3)-expressing cells. Small-animal PET/CT with (64)Cu-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.Together, these data suggest that (64)Cu-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.
- Subjects :
- Tail
Pathology
medicine.medical_specialty
Osteolysis
Leukemia, T-Cell
medicine.medical_treatment
H&E stain
Osteoclasts
Standardized uptake value
Bone Neoplasms
Article
Metastasis
Diagnosis, Differential
Mice
Osteoclast
medicine
Animals
Humans
Radiology, Nuclear Medicine and imaging
Receptors, Vitronectin
Diphosphonates
business.industry
Gene Products, tax
Bisphosphonate
medicine.disease
Spine
Gene Expression Regulation, Neoplastic
Leukemia
medicine.anatomical_structure
Zoledronic acid
Treatment Outcome
Copper Radioisotopes
Positron-Emission Tomography
business
Multiple Myeloma
Tomography, X-Ray Computed
Oligopeptides
medicine.drug
Subjects
Details
- ISSN :
- 15355667
- Volume :
- 50
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Journal of nuclear medicine : official publication, Society of Nuclear Medicine
- Accession number :
- edsair.doi.dedup.....73b35a0949a0af17df137dd402b163f9