Louie, A.Y. et al. In vivo visualization of gene expression using magnetic resonance imaging. Nat. Biotechnol. 18, 321−325

Division of Biology Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Nature Biotechnology (Impact Factor: 41.51). 04/2000; 18(3):321-5. DOI: 10.1038/73780
Source: PubMed


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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    • "Another important challenge for MR contrast agent design is to generate bioactivated and theranostic agents that can be used in complex, physiological conditions. Bioactivated MR agents can be utilized to report enzymatic activities [43, 44], gene expression (e.g., β-galactosidase [45], β-glucoronidase, caspases [46], metalloproteinases (MMPs) (e.g., [47, 48])) as well as signal transduction and intracellular messengers such as Ca2+ [49] and Zn2+ (e.g., [50, 51]). It was observed that currently all MR-based molecular imaging probes are for preclinical and investigational use only. "
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    • "Moreover, several nanoparticles such as gold nanoparticles [13, 14] and polymer-coated bismuth sulfide nanoparticles [15] have emerged as novel CT contrast agents for cancer detection. Similarly, some novel genetically encoded MRI contrast agents and advanced sequence technologies have been used to detect gene expression [16–19]. Finally, due to the advantages of cost, convenience (for CT), and safety (for MRI), both CT and MRI will be appropriate imaging techniques for imaging-omics integration. "
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