Bevacizumab inhibits breast cancer-induced osteolysis, surrounding soft tissue metastasis, and angiogenesis in rats as visualized by VCT and MRI.
The aim of this study was to evaluate the effect of an antiangiogenic treatment with the vascular endothelial growth factor antibody bevacizumab in an experimental model of breast cancer bone metastasis and to monitor osteolysis, soft tissue tumor, and angiogenesis in bone metastasis noninvasively by volumetric computed tomography (VCT) and magnetic resonance imaging (MRI). After inoculation of MDA-MB-231 human breast cancer cells into nude rats, bone metastasis was monitored with contrast-enhanced VCT and MRI from day 30 to day 70 after tumor cell inoculation, respectively. Thereby, animals of the treatment group (10 mg/kg bevacizumab IV weekly, n = 15) were compared with sham-treated animals (n = 17). Treatment with bevacizumab resulted in a significant difference versus control in osteolytic as well as soft tissue lesion sizes (days 50 to 70 and 40 to 70 after tumor cell inoculation, respectively; P < .05). This observation was paralleled with significantly reduced vascularization in the treatment group as shown by reduced increase in relative signal intensity in dynamic contrast-enhanced MRI from days 40 to 70 (P < .05). Contrast-enhanced VCT and histology confirmed decreased angiogenesis as well as new bone formation after application of bevacizumab. In conclusion, bevacizumab significantly inhibited osteolysis, surrounding soft tissue tumor growth, and angiogenesis in an experimental model of breast cancer bone metastasis as visualized by VCT and MRI.
Bäuerle
Tobias
T
Department of Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Hilbig
Heidegard
H
Bartling
Sönke
S
Kiessling
Fabian
F
Kersten
Astrid
A
Schmitt-Gräff
Annette
A
Kauczor
Hans-Ulrich
HU
Delorme
Stefan
S
Berger
Martin R
MR
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001859:Bone Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D054893:Cone-Beam Computed Tomography; D006801:Humans; D008279:Magnetic Resonance Imaging; D009389:Neovascularization, Pathologic; D010014:Osteolysis / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D011923:Rats, Nude; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab