PURPOSE: Aim of this study was to investigate the specific treatment effects of 
inhibiting αvβ3/αvβ5 integrins by cilengitide in an animal model of breast 
cancer bone metastases using dynamic (18)F-FDG PET and gene expression analysis.
METHODS: For this purpose, nude rats bearing bone metastases were treated with 
cilengitide, a small molecule inhibitor of αvβ3 and αvβ5 integrins, from day 30 
to 55 after tumor cell inoculation of MDA-MB-231 breast cancer cells (25 mg/kg, 
5 days per week; n = 8 rats) and compared to control rats (n = 8). Dynamic 
(18)F-FDG PET data were assessed at days 30, 35 and 55 after tumor cell 
inoculation determining the vascular fraction VB and the metabolic variables 
k1-k4. At day 55, genome-wide mRNA expression analysis was performed to assess 
the treatment-specific expression changes from cilengitide-treated and control 
rats.
RESULTS: In a longitudinal (18)F-FDG PET study, the vascular fraction VB was 
significantly decreased in bone metastases between days 30/35, 30/55 and 35/55, 
whereas the kinetic parameters k1 and k4 were significantly decreased between 
days 30/55 in skeletal lesions of treated animals. Gene expression analysis from 
bone metastases at day 55 revealed that tumor-produced integrins (αvβ5) as well 
as factors relevant for angiogenesis (αvβ3, VEGF, PDGF), bone resorption (PTHrP 
and RANKL), extracellular matrix remodeling (collagen, CD44) and bone marrow 
microenvironment (CXCR4) were significantly reduced upon therapy with 
cilengitide.
CONCLUSIONS: Here, we provide evidence that cilengitide inhibits pivotal factors 
of all compartments of bone metastases including tumor cells, vasculature and 
bone microenvironment in vivo and by whole-genome transcriptome analysis.