Pharmacokinetics of BPA in gliomas with ultrasound induced blood-brain barrier disruption as measured by microdialysis

Feng-Yi Yang; Yi-Li Lin; Fong-In Chou; Yu-Chuan Lin; Yen-Wan Hsueh Liu; Lun-Wei Chang; Yu-Ling Hsieh

doi:10.1371/journal.pone.0100104

Pharmacokinetics of BPA in gliomas with ultrasound induced blood-brain barrier disruption as measured by microdialysis

PLoS One. 2014 Jun 17;9(6):e100104. doi: 10.1371/journal.pone.0100104. eCollection 2014.

Authors

Feng-Yi Yang¹, Yi-Li Lin², Fong-In Chou³, Yu-Chuan Lin⁴, Yen-Wan Hsueh Liu⁴, Lun-Wei Chang², Yu-Ling Hsieh²

Affiliations

¹ Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan.
² Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
³ Nuclear Science and Technology Development Center, National Tsing Hua University, Hsinchu City, Taiwan; Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu City, Taiwan.
⁴ Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu City, Taiwan.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood-Brain Barrier / injuries*
Boron Compounds / administration & dosage
Boron Compounds / pharmacokinetics*
Brain Neoplasms / metabolism*
Drug Delivery Systems*
Fructose / administration & dosage
Fructose / analogs & derivatives*
Fructose / pharmacokinetics
Glioma / metabolism*
Male
Microdialysis
Rats
Sound*

Substances

4-boronophenylalanine-fructose
Boron Compounds
Fructose

Grants and funding

This study was supported by grants from the National Science Council of Taiwan (no. NSC 102-2221-E-010-005-MY3 and NSC 101-2320-B-010-036-MY3), Cheng Hsin General Hospital Foundation (no. 102F218C11 and 103F003C17), Biophotonics & Molecular Imaging Research Center, and the Ministry of Education, Aim for the Top University Plan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.