MRI-guided focused ultrasound drug delivery to DMG tumors in a mouse model

Diffuse midline glioma (DMG) is the most common and unfortunately the most deadly brainstem tumor in childern. Current clincal treatment methods only involve palliative radiotherapy that does not significantly improve survival beyond its poor mean survival of 9 months. These tumors remain difficult to treat with chemotherapy as they maintain an intact blood brain barrier (BBB). Focused ultrasound (FUS) and microbubbles (MBs) has been shown to disrupt the BBB, allowing chemotherapeutics to enter the perenchyma. Panobinostat is one of the chemotherapeutics that has difficulty crossing the BBB, although it has promising effects in vitro. In this study, we hypothesized that MB + FUS could disrupt the BBB, allowing a higher concentration of Panobinostat to enter the tumor region and provide a therapeutic effect. Our results demonstrate that MB + FUS can successfully deliver Panobinostat to the pons with DMG tumors over 3-fold, while only slightly increasing the concentration of the forebrain. Passive cavitation detection during treatments showed harmonic cavitation throughout the 3-minute treatment, while not having any significant broadband cavitation. The combination of both Panobinostat and MB + FUS showed major decreases in tumor growth by ∼71% by the end of the treatment weeks when compared to Panobinostat alone. A significant survival benefit was also demonstrated.