In vivo visualization of gene expression using magnetic resonance imaging. Nat Biotechnol

Division of Biology Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Nature Biotechnology (Impact Factor: 39.08). 04/2000; 18(3):321-5. DOI: 10.1038/73780
Source: PubMed

ABSTRACT High-resolution in vivo imaging of gene expression is not possible in opaque animals by existing techniques. Here we present a new approach for obtaining such images by magnetic resonance imaging (MRI) using an MRI contrast agent that can indicate reporter gene expression in living animals. We have prepared MRI contrast agents in which the access of water to the first coordination sphere of a chelated paramagnetic ion is blocked with a substrate that can be removed by enzymatic cleavage. Following cleavage, the paramagnetic ion can interact directly with water protons to increase the MR signal. Here, we report an agent where galactopyranose is the blocking group. This group renders the MRI contrast agent sensitive to expression of the commonly used marker gene, beta-galactosidase. To cellular resolution, regions of higher intensity in the MR image correlate with regions expressing marker enzyme. These results offer the promise of in vivo mapping of gene expression in transgenic animals and validate a general approach for constructing a family of MRI contrast agents that respond to biological activity.

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Available from: Rex A Moats, Aug 17, 2015
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    • "Finally, enzyme based contrast agents combining MRI contrast with in situ chemical processing. An early example visualized βgalactosidase expression via enzymatic hydrolysis of a Gadolinium substrate [125]. Given the mature level of this technology incremental development of molecular targeted contrast agents will occur. "
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    • "Many of these contrast agents are lanthanide chelates that require direct interaction of water with the lanthanide ion. If this interaction is prevented by a functional group that can be removed by the targeted enzyme, the expression of this enzyme can be visualized by the responsive contrast agent (Himmelreich et al., 2006; Louie et al., 2000). We focus in this report on a new MRI contrast agent to visualize specifically inhibitory neurons, which use gamma-Aminobutyric acid (GABA) as a neurotransmitter. "
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