Blood-brain barrier disruption with focused ultrasound enhances delivery of dopamine transporter tracer (PE2I) into the brain
Résumé
PE2I is one of the most selective ligands for dopamine transporter. However it is associated with blood-brain barrier (BBB) permeability limitations. The aim of this study was to investigate the use of ultrasound and microbubbles to increase its delivery through the BBB and by determining the optimal experimental conditions that achieve a transient and safe BBB disruption. First, we stablished the ultrasound conditions that achieved a transient BBB disruption in rats using a non-permeant marker, Evans blue. Hence SonoVue® (450μL/kg) and Evans blue (100mg/kg) were intravenously administered. BBB leakage was obtained using ultrasound insonation through the rat skull at 1.6MPa, PRF 1Hz, duty cycle 1%, burst 10ms during 120sec. BBB disruption was observed in all treated animals (N=4) by histological analysis. The same experimental conditions were applied to enhance brain uptake of PE2I. Biological samples were analyzed using a scintillation counter apparatus. The results showed 50% and 20% increase of 125I-PE2I uptake in the striatum and cerebral cortex, respectively, in the treated rats (N=5) versus control (N=4). Similar enhancements were observed using SonoVue® at half concentration. This innovative method provides a great potential for intracerebral delivery of molecular ligands that could be used for the therapy of brain diseases.
Domaines
Acoustique [physics.class-ph]
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