Pharmacokinetics of BPA in gliomas with ultrasound induced blood-brain barrier disruption as measured by microdialysis.
Authors: Yang FY, Lin YL, Chou FI, Lin YC, Hsueh Liu YW, Chang LW, Hsieh YL
The blood-brain barrier (BBB) can be transiently disrupted by focused ultrasound (FUS) in the presence of microbubbles for targeted drug delivery. Previous studies have illustrated the pharmacokinetics of drug delivery across the BBB after sonication using indirect visualization techniques. In this study, we investigated the in vivo extracellular kinetics of boronophenylalanine-fructose (BPA-f) in glioma-bearing rats with FUS-induced BBB disruption by microdialysis. After simultaneous intravenous administration of BPA and FUS exposure, the boron concentration in the treated brains was quantified by inductively coupled plasma mass spectroscopy. With FUS, the mean peak concentration of BPA-f in the glioma dialysate was 3.6 times greater than without FUS, and the area under the concentration-time curve was 2.1 times greater. This study demonstrates that intracerebral microdialysis can be used to assess local BBB transport profiles of drugs in a sonicated site. Applying microdialysis to the study of metabolism and pharmacokinetics is useful for obtaining selective information within a specific brain site after FUS-induced BBB disruption.
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
To evaluate the in vivo extracellular concentration–time profile and pharmacokinetics of boronophenylalanine-fructose in glioma-bearing rat brains following focused ultrasound-induced BBB disruption and to compare sonicated versus non‑sonicated tumors.
Animal model / Human subject
Rats (glioma-bearing); strain: Fischer 344; age not specified; sex: male
Disease model
f98 glioma
MRI or image guidance method
Not specified in the provided text
Targeted brain region(s)
F98 Glioma
Target coordinates
5 mm posterior to bregma, 3 mm lateral, 5 mm depth
Cargo name and characteristics
Boronophenylalanine‑fructose (BPA‑f)
Route of administration
intravenous
Outcomes and Safety
Summary of Outcomes
Focused ultrasound-induced BBB disruption markedly increased delivery of BPA‑fructose to glioma extracellular fluid—producing ~3.6-fold higher peak boron, ~2.1-fold greater AUC and prolonged tumor retention—without altering plasma pharmacokinetics.
Duration of biological effect
5 h
Safety-related matter
The authors report that the microdialysis procedure during FUS-induced BBB disruption did not cause any severe side effects.
Brain Region
Ultrasound Parameters
Ultrasound instrument
1 MHz single-element focused transducer (A392S, Panametrics, Waltham, MA, USA)
FUS Frequency
1 MHz
FUS Intensity
Not reported in provided text
FUS Pressure
Not specified in the provided text
FUS Mode
pulsed
Pulse duration
50 ms
Duration of a single FUS session
60 s
Focal Characteristics
focal diameter: 3 mm, focal length: 26 mm
Treatment frequency
single session
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