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Impact of anti-angiogenic treatment on bone vascularization in a murine model of breast cancer bone metastasis using synchrotron radiation micro-CT
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  • hao xu,
  • Marie-Hèlène Lafage-Proust,
  • BOUAZZA Lamia,
  • Sandra Geraci,
  • Philippe Clezardin,
  • Bernard Roche,
  • Françoise Peyrin,
  • Max Langer
hao xu
Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé

Corresponding Author:[email protected]

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Marie-Hèlène Lafage-Proust
SAnté INgéniérie BIOlogie St-Etienne
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BOUAZZA Lamia
Physiopathologie Diagnostic et Traitements des Maladies Osseuses
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Sandra Geraci
Physiopathologie Diagnostic et Traitements des Maladies Osseuses
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Philippe Clezardin
INSERM U1033
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Bernard Roche
SAnté INgéniérie BIOlogie St-Etienne
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Françoise Peyrin
Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé
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Max Langer
Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé
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Abstract

Background and Purpose: Bone metastases are frequent complications of breast cancer, facilitate the development of anarchic vascularization and induce bone destruction. Therefore, anti-angiogenic drugs (AAD) have been tested as a therapeutic strategy for the treatment of breast cancer bone metastasis. However, the kinetics of skeletal vascularization in response to tumor invasion under AAD is still partially understood. Therefore, the aim of this study was to explore the effect of AAD on experimental bone metastasis by analyzing the three-dimensional (3D) bone vasculature during metastatic formation and progression. Experimental Approach: Eight-week-old female mice were treated with AAD (bevacizumab, vatalanib, or a combination of both drugs) or the vehicle (placebo) one day after injection with breast cancer cells. Mice were sacrificed 8 or 22 days after tumor cell inoculation (time points T1 and T2, respectively). Synchrotron radiation microcomputed tomography (SR-μCT) was used to image tibia with a contrast agent. 3D-bone and vascular networks were simultaneously visualized and quantitatively analyzed. Key Results: At T1, the trabecular bone volume was significantly increased in the combined AAD-treatment group, compared to the placebo- and single AAD-treatment groups. At T2, only the bone vasculature was reduced in the combined AAD-treatment group, as judged by measurement of the blood vessel thickness. Conclusion and Implications: We show for the first time that the use of SR-µCT with a contrast agent enables the simultaneous quantitative measurement of 3D bone and vessel microstructures, providing an unbiased method to assess the efficacy of targeted therapies in a mouse model of bone metastasis.