Ultrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer's Disease Mouse Models

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Ultrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer's Disease Mouse Models

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dc.contributor.author Raymond, Scott Bruce
dc.contributor.author Treat, Lisa H.
dc.contributor.author Dewey, Jonathan D.
dc.contributor.author McDannold, Nathan Judson
dc.contributor.author Hynynen, Kullervo
dc.contributor.author Bacskai, Brian
dc.date.accessioned 2011-04-18T01:21:48Z
dc.date.issued 2008
dc.identifier.citation Raymond, Scott B., Lisa H. Treat, Jonathan D. Dewey, Nathan J. McDannold, Kullervo Hynynen, and Brian J. Bacskai. 2008. Ultrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer's Disease Mouse Models. PLoS ONE 3(5): e2175. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4853400
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 of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0002175 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364662/pdf/ en_US
dash.license LAA
dc.subject biotechnology en_US
dc.subject bioengineering en_US
dc.subject neurological disorders en_US
dc.subject Alzheimer disease en_US
dc.subject radiology and medical imaging en_US
dc.subject magnetic resonance imaging en_US
dc.subject ultrasonography en_US
dc.title Ultrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer's Disease Mouse Models en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Bacskai, Brian
dc.date.available 2011-04-18T01:21:48Z
dash.affiliation.other HMS^Radiology-Brigham and Women's Hospital en_US
dash.affiliation.other HMS^Neurology-Massachusetts General Hospital en_US

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