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WIREs Nanomed Nanobiotechnol
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Ferritin nanoparticles as magnetic resonance reporter gene

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Abstract Dynamic imaging of gene expression in live animals is among the exciting challenges of molecular imaging. To achieve that, one of the approaches is to use reporter genes that encode for the synthesis of easily detectable products. Such reporter genes can be designed to be expressed under the control of the regulatory elements included in a promoter region of a gene of interest, thus allowing the use of the same reporter gene for the detection of multiple genes. The most commonly used reporter genes include the firefly light‐generating enzyme luciferase and the green fluorescent protein detectable by bioluminescence and fluorescence optical imaging, respectively. Over the last years a number of studies demonstrated the ability to use the iron‐binding protein ferritin as a reporter gene that allows the detection of gene expression by magnetic resonance imaging (MRI). MRI provides high spatial resolution and soft tissue contrast for deep tissues along with a large arsenal of functional and anatomical contrast mechanisms that can be correlated with gene expression, and can potentially be translated into clinical use Copyright © 2009 John Wiley & Sons, Inc. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

MRI detection of tetracycline‐regulated H‐ferritin expression (a) R2 relaxation rate maps of C6‐TET‐EGFP‐HA‐ferritin cells suspended in agarose with and without TET (5 days; 1µg/mL). (b) In vivo MRI detection of ferritin expression in C6‐TET‐EGFP‐HA‐ ferritin tumors in the hind limb of nude mice. TET was supplied in drinking water, starting 2 days before inoculation (colorbar–R2 values; scalebar = 2.5 mm). (Reprinted, with permission, from Ref. 63. Copyright 2005 Neoplasia Press, Inc.).

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MRI detection of H‐ferritin and Transferrin receptor overexpression. Transplanted iron‐loaded cells were detected in T*2‐weighted brain images. (a) Control (C17s) iron‐loaded cells. (b) Iron‐loaded cells overexpressing H‐ferritin and transferrin receptor (C17‐12s). (Reprinted, with permission, from Ref. 77. Copyright 2006 Wiley Periodicals, Inc.).

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MRI detection of H‐ferritin and L‐ferritin overexpression in the mouse brain. Adenovirus containing the MRI reporter was inoculated into the striatum. (a) T2‐weighted image 5 days after injection showing the inoculated sites (left arrows, MRI reporter; right arrow, AdV‐lacZ control). (b) X‐gal‐stained AdV‐lacZ transduction pattern at 5 days after inoculation. (Reprinted, with permission, from Ref. 64. Copyright 2005 Macmillan Publishers Ltd).

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MRI detection of endothelial overexpression of H‐ferritin in transgenic mice. Expression of ferritin was regulated by the VE‐cadherin promoter in double transgenic mice, but not in single transgenic siblings. Elevated R2 was observed in the liver and heart of E13.5 embryos studied in utero (a), and in the brain of adult mice (b). (Reprinted, with permission, from Ref. 33. Copyright 2007 Nature Publishing Group).

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