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Simple Summary: This study shows for the first time that the use of synchrotron radiation microcomputed tomography (SR-µCT) with a contrast agent enables the simultaneous quantitative measurement of three-dimensional (3D) bone and blood vessel microstructures in a murine model of breast cancer bone metastasis. Our data suggests that the combined anti-angiogenic drug (AAD) treatment (Bevacizumab + Vatalanib) dampens tumor-induced trabecular bone resorption and affects the 3D structure of bone microvascularization. The combined AAD might offer superior treatment to inhibit breast cancer bone metastasis in a mouse model. Bone metastases are frequent complications of breast cancer, facilitating 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. Seventy-three 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 eight or 22 days after tumor cell inoculation (time points T1 and T2, respectively). Synchrotron radiation microcomputed tomography (SR-μCT) was used to image bone and blood vessels with a contrast agent. Hence, 3D-bone and vascular networks were simultaneously visualized and quantitatively analyzed. At T1, the trabecular bone volume fraction was significantly increased (p < 0.05) 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 (p < 0.05), as judged by measurement of the blood vessel thickness. Our data suggest that, at the early stage, combined AAD treatment dampens tumor-induced bone resorption with no detectable effects on bone vessel organization while, at a later stage, it affects the structure of bone microvascularization. [ABSTRACT FROM AUTHOR]

Acoustic cavitation can improve local drug delivery in tumors. Without injected external nucleation agents, initiating inertial cavitation requires high negative pressures, which can lead to biological damage. In the present study, unseeded inertial cavitation was obtained in vivo using confocal beams, and the effect of these exposure conditions was assessed on drug structure and activity, shallow tissues and growth of breast tumors. No change was observed in the structure and cytotoxicity of doxorubicin. Experiments were conducted on healthy rats, exposing the thigh and abdomen. Histologic analyses at 72 h and 2 weeks post-treatment demonstrated a modest impact on tissues. Syngeneic 4 T1 breast tumors in mice were sonicated. Immunohistochemical analyses showed that ultrasound did not impact vascular density, proliferation and apoptosis of cancer cells. In addition, ultrasound did not negatively modify cancer cell spreading to the lungs and bone marrow. This provides evidence that these particular parameters can be used safely in vivo. [ABSTRACT FROM AUTHOR]