Evaluation of brain tumor vessels specific contrast agents for glioblastoma imaging

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DOIResolve DOI: http://doi.org/10.1093/neuonc/nor183
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Journal titleNeuro-Oncology
Pages5363; # of pages: 11
Subjectbinding protein; contrast medium; dextran; growth factor; nuclear magnetic resonance imaging agent; superparamagnetic iron oxide; vascular targeting agent; animal experiment; animal model; animal tissue; article; brain blood vessel; brain tumor; cancer tissue; controlled study; fluorescence microscopy; glioblastoma; in vivo study; infrared radiation; inoculation; male; mouse; near infrared spectroscopy; nonhuman; nuclear magnetic resonance imaging; relaxation time; Animals; Antibodies; Brain Neoplasms; Cell Line, Tumor; Contrast Media; Dextrans; Ferric Compounds; Glioblastoma; Humans; Insulin-Like Growth Factor Binding Proteins; Magnetic Resonance Imaging; Male; Mice; Mice, Nude; Microscopy, Fluorescence; Nanoparticles
AbstractA mouse model of glioblastoma multiforme was used to determine the accumulation of a targeted contrast agent in tumor vessels. The contrast agent, consisting of superparamagnetic iron oxide coated with dextran, was functionalized with an anti-insulin-like-growth-factor binding protein 7 (anti-IGFBP7) single domain antibody. The near infrared marker, Cy5.5, was also attached for an in vivo fluorescence study. A 9.4T magnetic resonance imaging (MRI) system was used for in vivo studies on days 10 and 11 following tumor inoculation. T2 relaxation time was used to measure the accumulation of the contrast agent in the tumor. Changes in tumor to brain contrast because of active targeting were compared with a nontargeted contrast agent. Effective targeting was confirmed with near infrared measurements and fluorescent microscopic analysis. The results showed that there was a statistically significant (P < .01) difference in normalized T2 between healthy brain and tumor tissue 10 min, 1 h, and 2 h point postinjection of the anti-IGFBP7 single domain antibody targeted and nontargeted iron oxide nanoparticles. A statistical difference remained in animals treated with targeted nanoparticles 24 h postinjection only. The MRI, near infrared imaging, and fluorescent microscopy studies showed corresponding spatial and temporal changes. We concluded that the developed anti-IGFBP7-iron oxide single domain antibodytargeted MRI contrast agent selectively binds to abnormal vessels within a glioblastoma. T2-weighted MRI and near infrared imaging are able to detect the targeting effects in brain tumors. © The Author(s) 2011.
Publication date
AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biodiagnostics (IBD-IBD); NRC Institute for Biological Sciences (IBS-ISB)
Peer reviewedYes
NPARC number21269457
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Record identifiere53e0f53-9eaf-4f78-8e84-5b7a98eff04d
Record created2013-12-12
Record modified2016-05-09
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