Site-specific opening of the blood-brain barrier.
Authors: Madsen SJ, Hirschberg H
The blood-brain barrier (BBB) poses a significant impediment for the delivery of therapeutic drugs into the brain. This is particularly problematic for the treatment of malignant gliomas which are characterized by diffuse infiltration of tumor cells into normal brain where they are protected by a patent BBB. Selective disruption of the BBB, followed by administration of anti-cancer agents, represents a promising approach for the elimination of infiltrating glioma cells. A summary of the techniques (focused ultrasound, photodynamic therapy and photochemical internalization) for site-specific opening of the BBB will be discussed in this review. Each approach is capable of causing localized and transient opening of the BBB with minimal damage to surrounding normal brain as evidenced from magnetic resonance images and histology.
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
To review and summarize techniques for site-specific, transient disruption of the blood–brain barrier (focused ultrasound, photodynamic therapy, and photochemical internalization) to enable delivery of anti-cancer agents to infiltrating glioma cells.
Animal model / Human subject
rat, Fischer 344, 150–200 g, not reported
Disease model
malignant glioma
MRI or image guidance method
Not specified; the paper reports T1-weighted contrast-enhanced MRI to demonstrate focal BBB opening after treatment, but does not describe how FUS targeting was guided.
Targeted brain region(s)
Glioma
Outcomes and Safety
Summary of Outcomes
0.69 MHz FUS with microbubbles induces site-specific, transient BBB disruption in a rat glioma model.
Duration of biological effect
4h
Safety-related matter
Low pressure (0.3 MPa) showed no significant pathology on histology.
Brain Region
Ultrasound Parameters
Ultrasound instrument
RK-100, FUS Instruments
FUS Frequency
0.69 MHz
FUS Intensity
0.8 MPa
FUS Pressure
Not reported
FUS Mode
not specified
Pulse duration
10 ms
Duration of a single FUS session
60 s
Treatment frequency
single session
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