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Enhancement in blood-tumor barrier permeability and delivery of liposomal doxorubicin using focused ultrasound and microbubbles: evaluation during tumor progression in a rat glioma model This content has been downloaded from IOPscience. Please scroll down to see the full text. 2015 Phys. Med. Biol. 60 2511 (http://iopscience.iop.org/0031-9155/60/6/2511) View the table of contents for this issue, or go to the journal homepage for more
Download details: IP Address: 61.129.42.15 This content was downloaded on 07/05/2015 at 06:54
Please note that terms and conditions apply.
Institute of Physics and Engineering in Medicine Phys. Med. Biol. 60 (2015) 2511–2527
Physics in Medicine & Biology doi:10.1088/0031-9155/60/6/2511
Enhancement in blood-tumor barrier permeability and delivery of liposomal doxorubicin using focused ultrasound and microbubbles: evaluation during tumor progression in a rat glioma model Muna Aryal1,2, Juyoung Park3, Natalia Vykhodtseva2, Yong-Zhi Zhang2 and Nathan McDannold2 1
Department of Physics, Boston College, 221 Longwood Avenue, Boston, MA 02115, USA 2 Department of Radiology, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA 3 Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea E-mail: [email protected] Received 23 September 2014, revised 4 February 2015 Accepted for publication 6 February 2015 Published 6 March 2015 Abstract
Effective drug delivery to brain tumors is often challenging because of the heterogeneous permeability of the ‘blood tumor barrier’ (BTB) along with other factors such as increased interstitial pressure and drug efflux pumps. Focused ultrasound (FUS) combined with microbubbles can enhance the permeability of the BTB in brain tumors, as well as the blood–brain barrier in the surrounding tissue. In this study, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to characterize the FUS-induced permeability changes of the BTB in a rat glioma model at different times after implantation. 9L gliosarcoma cells were implanted in both hemispheres in male rats. At day 9, 14, or 17 days after implantation, FUS-induced BTB disruption using 690 kHz ultrasound and definity microbubbles was performed in one tumor in each animal. Before FUS, liposomal doxorubicin was administered at a dose of 5.67 mg kg−1. This chemotherapy agent was previously shown to improve survival in animal glioma models. The transfer coefficient Ktrans describing extravasation of the MRI contrast agent Gd-DTPA was measured via DCE-MRI before and after sonication. We found that tumor doxorubicin concentrations increased monotonically (823 ± 600, 1817 ± 732 and 2432 ± 448 ng g−1) in the control tumors at 9, 14 and 17 d. 0031-9155/15/062511+17$33.00 © 2015 Institute of Physics and Engineering in Medicine Printed in the UK
2511
M Aryal et al
Phys. Med. Biol. 60 (2015) 2511
With FUS-induced BTB disruption, the doxorubicin concentrations were enhanced significantly (P
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My IOPscience
Enhancement in blood-tumor barrier permeability and delivery of liposomal doxorubicin using focused ultrasound and microbubbles: evaluation during tumor progression in a rat glioma model This content has been downloaded from IOPscience. Please scroll down to see the full text. 2015 Phys. Med. Biol. 60 2511 (http://iopscience.iop.org/0031-9155/60/6/2511) View the table of contents for this issue, or go to the journal homepage for more
Download details: IP Address: 61.129.42.15 This content was downloaded on 07/05/2015 at 06:54
Please note that terms and conditions apply.
Institute of Physics and Engineering in Medicine Phys. Med. Biol. 60 (2015) 2511–2527
Physics in Medicine & Biology doi:10.1088/0031-9155/60/6/2511
Enhancement in blood-tumor barrier permeability and delivery of liposomal doxorubicin using focused ultrasound and microbubbles: evaluation during tumor progression in a rat glioma model Muna Aryal1,2, Juyoung Park3, Natalia Vykhodtseva2, Yong-Zhi Zhang2 and Nathan McDannold2 1
Department of Physics, Boston College, 221 Longwood Avenue, Boston, MA 02115, USA 2 Department of Radiology, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA 3 Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea E-mail: [email protected] Received 23 September 2014, revised 4 February 2015 Accepted for publication 6 February 2015 Published 6 March 2015 Abstract
Effective drug delivery to brain tumors is often challenging because of the heterogeneous permeability of the ‘blood tumor barrier’ (BTB) along with other factors such as increased interstitial pressure and drug efflux pumps. Focused ultrasound (FUS) combined with microbubbles can enhance the permeability of the BTB in brain tumors, as well as the blood–brain barrier in the surrounding tissue. In this study, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to characterize the FUS-induced permeability changes of the BTB in a rat glioma model at different times after implantation. 9L gliosarcoma cells were implanted in both hemispheres in male rats. At day 9, 14, or 17 days after implantation, FUS-induced BTB disruption using 690 kHz ultrasound and definity microbubbles was performed in one tumor in each animal. Before FUS, liposomal doxorubicin was administered at a dose of 5.67 mg kg−1. This chemotherapy agent was previously shown to improve survival in animal glioma models. The transfer coefficient Ktrans describing extravasation of the MRI contrast agent Gd-DTPA was measured via DCE-MRI before and after sonication. We found that tumor doxorubicin concentrations increased monotonically (823 ± 600, 1817 ± 732 and 2432 ± 448 ng g−1) in the control tumors at 9, 14 and 17 d. 0031-9155/15/062511+17$33.00 © 2015 Institute of Physics and Engineering in Medicine Printed in the UK
2511
M Aryal et al
Phys. Med. Biol. 60 (2015) 2511
With FUS-induced BTB disruption, the doxorubicin concentrations were enhanced significantly (P
