Ultrasound-induced opening of the blood-brain barrier to enhance temozolomide and irinotecan delivery: an experimental study in rabbits

OBJECT The blood-brain barrier (BBB) limits the intracerebral penetration of drugs and brain tumor treatment efficacy. The effect of ultrasound-induced BBB opening on the intracerebral concentration of temozolomide(TMZ) and irinotecan(CPT-11) was assessed. METHODS This study was performed using 34 healthy New Zealand rabbits. Half had unilateral BBB opening, and half served as controls. Sonicationswere performed by pulsing a 1.05-MHz planar ultrasound transducer with a duty cycle of 2.5% and an in situ acoustic pressure level of 0.6 MPa after injection of a microbubbleultrasound contrast agent. Drugs were injected either 5 minutes before (ChemoPreUS) or 15 minutes after (ChemoPostUS) the ultrasound sonication. The plasma and intracerebral concentrations of both drugs were quantified using ultra-performance liquid chromatography. RESULTS The mean intracerebral tissue-to-plasma drug concentration ratioin the control hemispheres was 34% for TMZ and 2% for CPT-11. After BBB opening, these values increase...