Science Times: Focused Ultrasound Enhances Central Nervous System Delivery of Bevacizumab for Malignant Glioma Treatment

Glioblastoma multiforme is a highly vascularized tumor with a high degree of angiogenesis resulting from high levels of vascular endothelial growth factor (VEGF). Bevacizumab is a humanized monoclonal antibody that binds to VEGF-A and inhibits endothelial cell proliferation, thus reducing tumor neovascularization. In principle, steady administration of antiangiogenic chemotherapy should impede vascular development and deprive a tumor of its nutrients, thus impeding its growth. However, these effects are mitigated by the reduction of vascular permeability by anti-VEGF medications, which transiently restores normalcy to the blood-brain barrier (BBB), thereby reducing further penetration of bevacizumab through the BBB and into brain parenchyma. This ultimately reduces the antiangiogenic efficacy of bevacizumab.

On the basis of previous studies of the ability of the BBB to be disrupted by focused ultrasound1 and to allow the passage of chemotherapeutic agents,2 Liu et al3 hypothesized that focused ultrasound could be used to temporarily disrupt the BBB and to allow consistent penetration of the BBB by bevacizumab. They divided their experiment into 2 parts. First, they assessed whether focused ultrasound generated BBB disruption sufficient enough to enhance bevacizumab penetration in healthy mice and to determine the appropriate focused ultrasound dose. They found that pressure levels of 0.4 MPa (an intermediate exposure) and 0.8 MPa (aggressive exposure) resulted in a 5.73-fold and 56.77-fold increase, respectively, in intraparenchymal bevacizumab concentrations compared with controls not exposed to focused ultrasound.

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