Pharmacodynamic Analysis of Magnetic Resonance Imaging-Monitored Focused Ultrasound-Induced Blood-Brain Barrier Opening for Drug Delivery to Brain Tumors
Journal
BioMed Research International
Journal Volume
2013
Pages
627496
Date Issued
2013
Author(s)
Abstract
Microbubble-enhanced focused ultrasound (FUS) can enhance the delivery of therapeutic agents into the brain for brain tumor treatment. The purpose of this study was to investigate the influence of brain tumor conditions on the distribution and dynamics of small molecule leakage into targeted regions of the brain after FUS-BBB opening. A total of 34 animals were used, and the process was monitored by 7T-MRI. Evans blue (EB) dye as well as Gd-DTPA served as small molecule substitutes for evaluation of drug behavior. EB was quantified spectrophotometrically. Spin-spin (R1) relaxometry and area under curve (AUC) were measured by MRI to quantify Gd-DTPA. We found that FUS-BBB opening provided a more significant increase in permeability with small tumors. In contrast, accumulation was much higher in large tumors, independent of FUS. The AUC values of Gd-DTPA were well correlated with EB delivery, suggesting that Gd-DTPA was a good indicator of total small-molecule accumulation in the target region. The peripheral regions of large tumors exhibited similar dynamics of small-molecule leakage after FUS-BBB opening as small tumors, suggesting that FUS-BBB opening may have the most significant permeability-enhancing effect on tumor peripheral. This study provides useful information toward designing an optimized FUS-BBB opening strategy to deliver small-molecule therapeutic agents into brain tumors. © 2013 Po-Chun Chu et al.
Other Subjects
Evans blue; gadolinium pentetate; gadolinium pentetate meglumine; antineoplastic agent; Evans blue; gadolinium pentetate; animal cell; animal experiment; animal model; area under the curve; article; blood brain barrier; brain region; brain tumor; contrast enhancement; controlled study; drug accumulation; drug delivery system; drug distribution; echography; focused ultrasound; glioma; male; nonhuman; nuclear magnetic resonance imaging; rat; tumor volume; animal; brain tumor; human; nuclear magnetic resonance imaging; pathology; radiation exposure; radiography; sound; Animals; Antineoplastic Agents; Blood-Brain Barrier; Brain Neoplasms; Drug Delivery Systems; Evans Blue; Gadolinium DTPA; Humans; Magnetic Resonance Imaging; Rats; Sound
Type
journal article