In vivo visualization of gene expression using magnetic resonance imaging

Angelique Y. Louie, Martina M. Hüber, Eric T. Ahrens, Ute Rothbächer, Rex Moats, Russell E. Jacobs, Scott E. Fraser, Thomas J. Meade*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1016 Scopus citations

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, β-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.

Original languageEnglish (US)
Pages (from-to)321-325
Number of pages5
JournalNature biotechnology
Volume18
Issue number3
DOIs
StatePublished - 2000

Keywords

  • Contrast agent
  • Gadolinium
  • Gene expression
  • LacZ
  • MRI
  • β-galactosidase

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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