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dc.contributor.author Dewey, Jonathan D. en_US
dc.date.accessioned 2011-06-21T17:31:23Z
dc.date.available 2011-06-21T17:31:23Z
dc.date.issued 2008 en_US
dc.identifier.citation Raymond,Scott B.;Treat,Lisa H.;Dewey,Jonathan D.;McDannold,Nathan J.;Hynynen,Kullervo;Bacskai,Brian J.. 2008. Ultrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer's Disease Mouse Models. Plos One 3(5): e2175-e2175. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://hdl.handle.net/10161/4493
dc.description.abstract Alzheimer's disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques. We administered intravenous Trypan blue, an amyloid staining red fluorophore, and anti-amyloid antibodies, concurrently with focused ultrasound therapy in plaque-bearing, transgenic mouse models of Alzheimer's disease with amyloid pathology. MRI guidance permitted selective treatment and monitoring of plaque-heavy anatomical regions, such as the hippocampus. Treated brain regions exhibited 16.5 +/- 5.4-fold increase in Trypan blue fluorescence and 2.7 +/- 1.2-fold increase in anti-amyloid antibodies that localized to amyloid plaques. Ultrasound-enhanced delivery was consistently reproduced in two different transgenic strains (APPswe:PSEN1dE9, PDAPP), across a large age range (9-26 months), with and without MR guidance, and with little or no tissue damage. Ultrasound-mediated, transient blood-brain barrier disruption allows the delivery of both therapeutic and molecular imaging agents in Alzheimer's mouse models, which should aid pre-clinical drug screening and imaging probe development. Furthermore, this technique may be used to deliver a wide variety of small and large molecules to the brain for imaging and therapy in other neurodegenerative diseases. en_US
dc.language.iso en_US en_US
dc.publisher PUBLIC LIBRARY SCIENCE en_US
dc.relation.isversionof doi:10.1371/journal.pone.0002175 en_US
dc.subject biology en_US
dc.subject multidisciplinary sciences en_US
dc.title Ultrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer's Disease Mouse Models en_US
dc.title.alternative en_US
dc.description.version Version of Record en_US
duke.date.pubdate 2008-5-14 en_US
duke.description.endpage e2175 en_US
duke.description.issue 5 en_US
duke.description.startpage e2175 en_US
duke.description.volume 3 en_US
dc.relation.journal Plos One en_US

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