Reversibility of FUS-aided blood-tumor barrier opening for the delivery of therapeutics.

Abstract

Focused ultrasound (FUS) offers reversible disruption of the blood-brain barrier (BBB), which enables drug delivery to the brain. However, the impact of FUS on the blood-tumor barrier (BTB) remains largely misunderstood. The reversibility of FUS-induced BTB opening was monitored using PET imaging in a glioblastoma model. C57Bl/6 mice with bilateral GL261-GFP tumors received FUS specifically targeting the right hemisphere, followed by injections of the BBB permeability marker [18F]Fluoro-deoxysorbitol (183 Da) or the radiolabeled antibody [18F]avelumab (150 kDa). PET acquisitions where performed after 1h, 24h and 72h post-FUS. The uptake of [18F]avelumab and [18F]Fluoro-deoxysorbitol was increased immediately after FUS. At 24h post-FUS, BTB permeability returned to baseline as evidenced by consistent [18F]avelumab distribution volumes (VT) between tumors. By 72h, increased radiotracer uptake indicated tumor progression. These findings highlight the potential of FUS to enhance the brain delivery of therapeutics while preserving the BTB integrity over time.