| Targeted signal-amplifying enzymes enhance MRI of EGFR expression in an orthotopic model of human glioma. | |
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MedLine Citation:
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PMID: 21245103 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Epidermal growth factor receptor (EGFR) imaging in brain tumors is essential to visualize overexpression of EGFRvIII variants as a signature of highly aggressive gliomas and to identify patients that would benefit from anti-EGFR therapy. Seeking imaging improvements, we tested a novel pretargeting approach that relies on initial administration of enzyme-linked anti-EGFR monoclonal antibodies (mAb; EMD72000) followed by administration of a low-molecular-weight paramagnetic molecule (diTyr-GdDTPA) retained at the site of EGFR mAb accumulation. We hypothesized that diTyr-GdDTPA would become enzyme activated and retained on cells due to binding to tissue proteins. In support of this hypothesis, mAb-enzyme conjugates reacted with both membrane-isolated wild-type (wt) EGFR and EGFRvIII, but they bound primarily to EGFRvIII-expressing cells and not to EGFRwt-expressing cells. In vivo analysis of magnetic resonance (MR) tumor signal revealed differences in MR signal decay following diTyr-GdDTPA substrate administration. These differences were significant in that they suggested differences in substrate elimination from the tissue which relied on the specificity of the initial mAb binding: a biexponential signal decay was observed in tumors only upon preinjection with EGFR-targeted conjugates. Endpoint MRI in this setting revealed detailed images of tumors which correlated with immunohistochemical detection of EGFR expression. Together, our findings suggest an improved method to identify EGFRvIII-expressing gliomas in vivo that are best suited for treatment with therapeutic EGFR antibodies. |
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Authors:
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Mohammed S Shazeeb; Christopher H Sotak; Michael DeLeo; Alexei Bogdanov |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-01-18 |
Journal Detail:
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Title: Cancer research Volume: 71 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-03-16 Completed Date: 2011-07-25 Revised Date: 2012-03-19 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 2230-9 Citation Subset: IM |
Copyright Information:
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©2011 AACR. |
Affiliation:
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Department of Biomedical Engineering, Worcester Polytechnic Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / chemistry, metabolism Antibodies, Monoclonal, Humanized Brain Neoplasms / genetics, metabolism*, pathology Cell Line, Tumor Gadolinium DTPA / chemistry, metabolism Glioma / genetics, metabolism*, pathology Horseradish Peroxidase / chemistry, metabolism Humans Image Enhancement Magnetic Resonance Imaging / methods* Mutation Neoplasm Transplantation Rats Rats, Nude Receptor, Epidermal Growth Factor / chemistry, genetics, metabolism* Reproducibility of Results Signal Processing, Computer-Assisted Transplantation, Heterologous |
| Grant Support | |
ID/Acronym/Agency:
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5R01EB000858/EB/NIBIB NIH HHS; R01 AG034901-02/AG/NIA NIH HHS; R01 EB000858-09/EB/NIBIB NIH HHS; R21 NS061132-02S1/NS/NINDS NIH HHS; R33 CA134385-03/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/epidermal growth factor receptor VIII; 0/matuzumab; 80529-93-7/Gadolinium DTPA; EC 1.11.1.-/Horseradish Peroxidase; EC 2.7.10.1/Receptor, Epidermal Growth Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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