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 were performed at 1 h, 24 h and 72 h post-FUS. The uptake of [18F]avelumab and [18F]fluoro-deoxysorbitol increased immediately after FUS. At 24 h post-FUS, BTB permeability returned to the baseline, as evidenced by consistent [18F]avelumab distribution volumes (VT) between tumors. By 72 h, increased radiotracer uptake indicated tumor progression. These findings highlight the potential of FUS to enhance the delivery of therapeutics to the brain while preserving BTB integrity over time.