Improved Anti-Tumor Effect of Liposomal Doxorubicin After Targeted Blood-Brain Barrier Disruption by MRI-Guided Focused Ultrasound in Rat Glioma
Abstract The blood-brain barrier (BBB) inhibits the entry of the majority of chemotherapeutic agents into the brain. Previous studies have illustrated the feasibility of drug delivery across the BBB using focused ultrasound (FUS) and microbubbles. Here, we investigated the effect of FUS-enhanced del...
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| Veröffentlicht in: | Ultrasound in medicine & biology 2012-10, Vol.38 (10), p.1716-1725 |
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| creator | Treat, Lisa H McDannold, Nathan Zhang, Yongzhi Vykhodtseva, Natalia Hynynen, Kullervo |
| description | Abstract The blood-brain barrier (BBB) inhibits the entry of the majority of chemotherapeutic agents into the brain. Previous studies have illustrated the feasibility of drug delivery across the BBB using focused ultrasound (FUS) and microbubbles. Here, we investigated the effect of FUS-enhanced delivery of doxorubicin on survival in rats with and 9L gliosarcoma cells inoculated in the brain. Each rat received either: (1) no treatment (control; N = 11), (2) FUS only (N = 9), (3) IV liposomal doxorubicin (DOX only; N = 17), or (4) FUS with concurrent IV injections of liposomal doxorubicin (FUS+DOX; N = 20). Post-treatment by magnetic resonance imaging (MRI) showed that FUS+DOX reduced tumor growth compared with DOX only. Further, we observed a modest but significant increase in median survival time after a single treatment FUS+DOX treatment ( p = 0.0007), whereas neither DOX nor FUS had any significant impact on survival on its own. These results suggest that combined ultrasound-mediated BBB disruption may significantly increase the antineoplastic efficacy of liposomal doxorubicin in the brain. |
| doi_str_mv | 10.1016/j.ultrasmedbio.2012.04.015 |
| format | Article |
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Previous studies have illustrated the feasibility of drug delivery across the BBB using focused ultrasound (FUS) and microbubbles. Here, we investigated the effect of FUS-enhanced delivery of doxorubicin on survival in rats with and 9L gliosarcoma cells inoculated in the brain. Each rat received either: (1) no treatment (control; N = 11), (2) FUS only (N = 9), (3) IV liposomal doxorubicin (DOX only; N = 17), or (4) FUS with concurrent IV injections of liposomal doxorubicin (FUS+DOX; N = 20). Post-treatment by magnetic resonance imaging (MRI) showed that FUS+DOX reduced tumor growth compared with DOX only. Further, we observed a modest but significant increase in median survival time after a single treatment FUS+DOX treatment ( p = 0.0007), whereas neither DOX nor FUS had any significant impact on survival on its own. These results suggest that combined ultrasound-mediated BBB disruption may significantly increase the antineoplastic efficacy of liposomal doxorubicin in the brain.</description><identifier>ISSN: 0301-5629</identifier><identifier>EISSN: 1879-291X</identifier><identifier>DOI: 10.1016/j.ultrasmedbio.2012.04.015</identifier><identifier>PMID: 22818878</identifier><identifier>CODEN: USMBA3</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>9L gliosarcoma ; Animals ; Antineoplastic Agents - administration & dosage ; Biological and medical sciences ; Blood-brain barrier ; Blood-Brain Barrier - radiation effects ; Brain Neoplasms - diagnosis ; Brain Neoplasms - drug therapy ; Brain Neoplasms - physiopathology ; Cell Line, Tumor ; Doxorubicin ; Doxorubicin - administration & dosage ; Focused ultrasound ; Gliosarcoma - diagnosis ; Gliosarcoma - drug therapy ; Gliosarcoma - physiopathology ; Investigative techniques, diagnostic techniques (general aspects) ; Liposomes - administration & dosage ; Liposomes - chemistry ; Magnetic Resonance Imaging, Interventional - methods ; Male ; Medical sciences ; Microbubbles - therapeutic use ; Neurology ; Radiology ; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) ; Rats ; Rats, Sprague-Dawley ; Sonication - methods ; Survival ; Treatment Outcome ; Tumors of the nervous system. Phacomatoses</subject><ispartof>Ultrasound in medicine & biology, 2012-10, Vol.38 (10), p.1716-1725</ispartof><rights>World Federation for Ultrasound in Medicine & Biology</rights><rights>2012 World Federation for Ultrasound in Medicine & Biology</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.</rights><rights>2012 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. 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Previous studies have illustrated the feasibility of drug delivery across the BBB using focused ultrasound (FUS) and microbubbles. Here, we investigated the effect of FUS-enhanced delivery of doxorubicin on survival in rats with and 9L gliosarcoma cells inoculated in the brain. Each rat received either: (1) no treatment (control; N = 11), (2) FUS only (N = 9), (3) IV liposomal doxorubicin (DOX only; N = 17), or (4) FUS with concurrent IV injections of liposomal doxorubicin (FUS+DOX; N = 20). Post-treatment by magnetic resonance imaging (MRI) showed that FUS+DOX reduced tumor growth compared with DOX only. Further, we observed a modest but significant increase in median survival time after a single treatment FUS+DOX treatment ( p = 0.0007), whereas neither DOX nor FUS had any significant impact on survival on its own. These results suggest that combined ultrasound-mediated BBB disruption may significantly increase the antineoplastic efficacy of liposomal doxorubicin in the brain.</description><subject>9L gliosarcoma</subject><subject>Animals</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Biological and medical sciences</subject><subject>Blood-brain barrier</subject><subject>Blood-Brain Barrier - radiation effects</subject><subject>Brain Neoplasms - diagnosis</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Brain Neoplasms - physiopathology</subject><subject>Cell Line, Tumor</subject><subject>Doxorubicin</subject><subject>Doxorubicin - administration & dosage</subject><subject>Focused ultrasound</subject><subject>Gliosarcoma - diagnosis</subject><subject>Gliosarcoma - drug therapy</subject><subject>Gliosarcoma - physiopathology</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Liposomes - administration & dosage</subject><subject>Liposomes - chemistry</subject><subject>Magnetic Resonance Imaging, Interventional - methods</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microbubbles - therapeutic use</subject><subject>Neurology</subject><subject>Radiology</subject><subject>Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Sonication - methods</subject><subject>Survival</subject><subject>Treatment Outcome</subject><subject>Tumors of the nervous system. Phacomatoses</subject><issn>0301-5629</issn><issn>1879-291X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks1uEzEUhUcIREPgFZCFhMRmgn9mxh4WlZKmDZGCkEoqsbM8Hrs4zNjBHkfkLfrIdUgohRUrL-45517f72bZGwQnCKLq_WYSu8GL0Ku2MW6CIcITWEwgKp9kI8RoneMafX2ajSCBKC8rXJ9lL0LYQAhpRejz7AxjhhijbJTdLfutdzvVgqkdTL6OvfPgUmslB-A0WJmtC64XHZi7n87HxkhjwVQPyoO18LdqSM5Z51ybz7xIpZnw3qTi3AQft4NxFjR78Ol6mS-iaZP4yskY0nvz6wsu2hYk27UYwKIzqdPL7JkWXVCvTu84u7m6XF98zFefF8uL6SqXFWFDrhtdlrIpWyIFqzDRJawY0hozDRFpa1I0VS2loDUtKGV1rRVTqGBVSSiuNCPj7PyYu41NWqRUNs3T8a03vfB77oThf1es-cZv3Y6TgjDCaAp4dwrw7kdUYeC9CVJ1nbDKxcARJDUsYIEO0g9HqfQuBK_0QxsE-QEp3_DHSPkBKYcFT0iT-fXjQR-svxkmwduTQAQpOu2FlSb80VWkRDStaJzNjzqV1rpLkHiQRlmpWuMTbt4683_znP8TIztjTer8Xe1V2LjobQLHEQ_Jw78cjvBwgwhDiEtck3tTYt3v</recordid><startdate>20121001</startdate><enddate>20121001</enddate><creator>Treat, Lisa H</creator><creator>McDannold, Nathan</creator><creator>Zhang, Yongzhi</creator><creator>Vykhodtseva, Natalia</creator><creator>Hynynen, Kullervo</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20121001</creationdate><title>Improved Anti-Tumor Effect of Liposomal Doxorubicin After Targeted Blood-Brain Barrier Disruption by MRI-Guided Focused Ultrasound in Rat Glioma</title><author>Treat, Lisa H ; McDannold, Nathan ; Zhang, Yongzhi ; Vykhodtseva, Natalia ; Hynynen, Kullervo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c638t-fbf55cb5d3ca8623f50681ff28f013d934b69cca797477899fe8e148653726f83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>9L gliosarcoma</topic><topic>Animals</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Biological and medical sciences</topic><topic>Blood-brain barrier</topic><topic>Blood-Brain Barrier - radiation effects</topic><topic>Brain Neoplasms - diagnosis</topic><topic>Brain Neoplasms - drug therapy</topic><topic>Brain Neoplasms - physiopathology</topic><topic>Cell Line, Tumor</topic><topic>Doxorubicin</topic><topic>Doxorubicin - administration & dosage</topic><topic>Focused ultrasound</topic><topic>Gliosarcoma - diagnosis</topic><topic>Gliosarcoma - drug therapy</topic><topic>Gliosarcoma - physiopathology</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Liposomes - administration & dosage</topic><topic>Liposomes - chemistry</topic><topic>Magnetic Resonance Imaging, Interventional - methods</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microbubbles - therapeutic use</topic><topic>Neurology</topic><topic>Radiology</topic><topic>Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Sonication - methods</topic><topic>Survival</topic><topic>Treatment Outcome</topic><topic>Tumors of the nervous system. Phacomatoses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Treat, Lisa H</creatorcontrib><creatorcontrib>McDannold, Nathan</creatorcontrib><creatorcontrib>Zhang, Yongzhi</creatorcontrib><creatorcontrib>Vykhodtseva, Natalia</creatorcontrib><creatorcontrib>Hynynen, Kullervo</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Ultrasound in medicine & biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Treat, Lisa H</au><au>McDannold, Nathan</au><au>Zhang, Yongzhi</au><au>Vykhodtseva, Natalia</au><au>Hynynen, Kullervo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improved Anti-Tumor Effect of Liposomal Doxorubicin After Targeted Blood-Brain Barrier Disruption by MRI-Guided Focused Ultrasound in Rat Glioma</atitle><jtitle>Ultrasound in medicine & biology</jtitle><addtitle>Ultrasound Med Biol</addtitle><date>2012-10-01</date><risdate>2012</risdate><volume>38</volume><issue>10</issue><spage>1716</spage><epage>1725</epage><pages>1716-1725</pages><issn>0301-5629</issn><eissn>1879-291X</eissn><coden>USMBA3</coden><abstract>Abstract The blood-brain barrier (BBB) inhibits the entry of the majority of chemotherapeutic agents into the brain. Previous studies have illustrated the feasibility of drug delivery across the BBB using focused ultrasound (FUS) and microbubbles. Here, we investigated the effect of FUS-enhanced delivery of doxorubicin on survival in rats with and 9L gliosarcoma cells inoculated in the brain. Each rat received either: (1) no treatment (control; N = 11), (2) FUS only (N = 9), (3) IV liposomal doxorubicin (DOX only; N = 17), or (4) FUS with concurrent IV injections of liposomal doxorubicin (FUS+DOX; N = 20). Post-treatment by magnetic resonance imaging (MRI) showed that FUS+DOX reduced tumor growth compared with DOX only. Further, we observed a modest but significant increase in median survival time after a single treatment FUS+DOX treatment ( p = 0.0007), whereas neither DOX nor FUS had any significant impact on survival on its own. 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| subjects | 9L gliosarcoma Animals Antineoplastic Agents - administration & dosage Biological and medical sciences Blood-brain barrier Blood-Brain Barrier - radiation effects Brain Neoplasms - diagnosis Brain Neoplasms - drug therapy Brain Neoplasms - physiopathology Cell Line, Tumor Doxorubicin Doxorubicin - administration & dosage Focused ultrasound Gliosarcoma - diagnosis Gliosarcoma - drug therapy Gliosarcoma - physiopathology Investigative techniques, diagnostic techniques (general aspects) Liposomes - administration & dosage Liposomes - chemistry Magnetic Resonance Imaging, Interventional - methods Male Medical sciences Microbubbles - therapeutic use Neurology Radiology Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) Rats Rats, Sprague-Dawley Sonication - methods Survival Treatment Outcome Tumors of the nervous system. Phacomatoses |
| title | Improved Anti-Tumor Effect of Liposomal Doxorubicin After Targeted Blood-Brain Barrier Disruption by MRI-Guided Focused Ultrasound in Rat Glioma |
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