Cilengitide inhibits progression of experimental breast cancer bone metastases as imaged noninvasively using VCT, MRI and DCE-MRI in a longitudinal in vivo study.
The aim of this study was to investigate the effect of inhibiting αvβ(3)/α(v) β(5) integrins by cilengitide in experimentally induced breast cancer bone metastases using noninvasive imaging techniques. For this purpose, nude rats bearing established breast cancer bone metastases were treated with cilengitide, a small molecule inhibitor of αvβ(3) and αvβ(5) integrins (75 mg/kg, five days per week; n = 12 rats) and compared to vehicle-treated control rats (n = 12). In a longitudinal study, conventional magnetic resonance imaging (MRI) and flat panel volumetric computed tomography were used to assess the volume of the soft tissue tumor and osteolysis, respectively, and dynamic contrast-enhanced (DCE-) MRI was performed to determine functional parameters of the tumor vasculature reflecting blood volume and blood vessel permeability. In rats treated with cilengitide, VCT and MRI showed that osteolytic lesions and the respective bone metastatic soft tissue tumors progressed more slowly than in vehicle-treated controls. DCE-MRI indicated a decrease in blood volume and an increase in vessel permeability and immunohistology revealed increased numbers of immature vessels in cilengitide-treated rats compared to vehicle controls. In conclusion, treatment of experimental breast cancer bone metastases with cilengitide resulted in pronounced antiresorptive and antitumor effects, suggesting that αvβ(3)/αvβ(5) inhibition may be a promising therapeutic approach for bone metastases.
Bäuerle
Tobias
T
Department of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany. t.baeuerle@dkfz.de
Komljenovic
Dorde
D
Merz
Maximilian
M
Berger
Martin R
MR
Goodman
Simon L
SL
Semmler
Wolfhard
W
D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary*; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011923:Rats, Nude; D019030:Receptors, Vitronectin / Q000378:metabolism; D012910:Snake Venoms / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed / Q000379:methods*
D039302:Integrin alphaVbeta3; D019030:Receptors, Vitronectin; D012910:Snake Venoms; C064660:integrin alphaVbeta5; C422910:Cilengitide