Focused ultrasound (FUS) exposure with the presence of microbubbles has been shown to transiently open the blood-brain barrier (BBB), and thus has potential to enhance the delivery of various kinds of therapeutic agents into @entity1313 . The purpose of this study was to assess the preclinical therapeutic efficacy of FUS-BBB opening for enhanced @entity2903 ( @entity2904 ) delivery in @entity11 treatment. FUS exposure with microbubbles was delivered to open the BBB of @entity19 that were either normal or implanted with U87 @entity1 @entity11 cells. Different @entity2904 dose regimens were tested, ranging from 2.5 to 25 mg/kg. Plasma and brain samples were obtained at different time-points ranging from 0.5 to 4 hours, and the @entity2904 concentration within samples was quantitated via a developed LC-MS/MS procedure. @entity5 progression was followed with T2-MRI, and animal survival and brain tissue histology were conducted. Results demonstrated that FUS-BBB opening caused the local @entity2904 accumulation in the brain to increase from 6.98 to 19 ng/mg. @entity2904 degradation time in the @entity5 core was found to increase from 1.02 to 1.56 hours. Improved @entity5 progression and animal survival were found at different @entity2904 doses (up to 15% and 30%, respectively). In conclusion, this study provides preclinical evidence that FUS-BBB opening increases the local concentration of @entity2904 to improve the control of @entity5 progression and animal survival, suggesting the potential for clinical application to improve current @entity1313 treatment.

Pharmacodynamic and therapeutic investigation of focused ultrasound-induced blood-brain barrier opening for enhanced @entity2903 delivery in XXXX treatment.

@entity1 :: ('9606', 'Species') :: ['human'] @entity1313 :: ('MESH:D001932', 'Disease') :: ['brain tumor', 'brain tumors'] @entity19 :: ('10090', 'Species') :: ['nude mice'] @entity2904 :: ('CHEBI:72564', 'Chemical') :: ['TMZ'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'Tumor'] @entity11 :: ('MESH:D005910', 'Disease') :: ['glioma'] @entity2903 :: ('MESH:C047246', 'Chemical') :: ['temozolomide']
@entity11 :: (MESH:D005910,Disease) :: ['glioma']
