| Real-time MR imaging with Gadoteridol predicts distribution of transgenes after convection-enhanced delivery of AAV2 vectors. | |
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MedLine Citation:
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PMID: 20551915 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Gene therapies that utilize convention-enhanced delivery (CED) will require close monitoring of vector infusion in real time and accurate prediction of drug distribution. The magnetic resonance imaging (MRI) contrast agent, Gadoteridol (Gd), was used to monitor CED infusion and to predict the expression pattern of glial cell line-derived neurotrophic factor (GDNF) protein after administration of adeno-associated virus type 2 (AAV2) vector encoding human pre-pro-GDNF complementary DNA. The nonhuman primate (NHP) thalamus was utilized for modeling infusion to allow delivery of volumes more relevant to planned human studies. AAV2 encoding human aromatic L-amino acid decarboxylase (AADC) was coinfused with AAV2-GDNF/Gd to confirm regions of AAV2 transduction versus extracellular GDNF diffusion. There was a close correlation between Gd distribution and GDNF or AADC expression, and the ratios of expression areas of GDNF or AADC versus Gd were both close to 1. Our data support the use of Gd and MRI to monitor AAV2 infusion via CED and to predict the distribution of GDNF protein after AAV2-GDNF administration. |
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Authors:
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Xiaomin Su; Adrian P Kells; Ernesto A Salegio; Ernesto Aguilar Salegio; R Mark Richardson; Piotr Hadaczek; Janine Beyer; John Bringas; Philip Pivirotto; John Forsayeth; Krystof S Bankiewicz |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-15 |
Journal Detail:
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Title: Molecular therapy : the journal of the American Society of Gene Therapy Volume: 18 ISSN: 1525-0024 ISO Abbreviation: Mol. Ther. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-02 Completed Date: 2010-11-23 Revised Date: 2012-03-09 |
Medline Journal Info:
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Nlm Unique ID: 100890581 Medline TA: Mol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 1490-5 Citation Subset: IM |
Affiliation:
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Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94103, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics* Animals Aromatic-L-Amino-Acid Decarboxylases / genetics, metabolism Contrast Media / diagnostic use* Genetic Vectors / genetics Heterocyclic Compounds / diagnostic use* Humans Macaca mulatta Magnetic Resonance Imaging / methods* Organometallic Compounds / diagnostic use* |
| Grant Support | |
ID/Acronym/Agency:
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F32 NS064692-01/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Contrast Media; 0/Heterocyclic Compounds; 0/Organometallic Compounds; 112188-16-6/gadoteridol; EC 4.1.1.28/Aromatic-L-Amino-Acid Decarboxylases |
| Comments/Corrections | |
Erratum In:
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Mol Ther. 2012 Feb;20(2):468 Note: Salegio, Ernesto Aguilar [corrected to Salegio, Ernesto A] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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