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

doi:10.1038/73780

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

Chemistry

Research output: Contribution to journal › Article › peer-review

1063 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 language	English (US)
Pages (from-to)	321-325
Number of pages	5
Journal	Nature biotechnology
Volume	18
Issue number	3
DOIs	https://doi.org/10.1038/73780
State	Published - Mar 1 2000

Funding

The authors thank Chris Kintner for the pCS2+ cB-gal construct; C. LaBonne, R. Davis for the CS2P-nGFP construct; and Markus Friedrich for the pRc/RSV.ZL construct. This work was supported by the Biological Imaging Center of the Beckman Institute, National Institute of Health (AR42671), the National Institute of Child Health and Human Development, the National Center for Research Resources, and the Human Brain Project (with contributions from the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Science Foundation). A.L. and M.H. were supported in part by an award from the Caltech Grubstakes program and Research Corporation Technologies, Tucson, AZ. M.H. was also supported by a fellowship from the Deutsche Forschungsgemeinschaft.

Keywords

Contrast agent
Gadolinium
Gene expression
LacZ
MRI
β-galactosidase

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

Access to Document

10.1038/73780

Cite this

@article{02d628aa02ac414193036ee26707f780,

title = "In vivo visualization of gene expression using magnetic resonance imaging",

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.",

keywords = "Contrast agent, Gadolinium, Gene expression, LacZ, MRI, β-galactosidase",

author = "Louie, \{Angelique Y.\} and H{\"u}ber, \{Martina M.\} and Ahrens, \{Eric T.\} and Ute Rothb{\"a}cher and Rex Moats and Jacobs, \{Russell E.\} and Fraser, \{Scott E.\} and Meade, \{Thomas J.\}",

note = "Funding Information: The authors thank Chris Kintner for the pCS2+ cB-gal construct; C. LaBonne, R. Davis for the CS2P-nGFP construct; and Markus Friedrich for the pRc/RSV.ZL construct. This work was supported by the Biological Imaging Center of the Beckman Institute, National Institute of Health (AR42671), the National Institute of Child Health and Human Development, the National Center for Research Resources, and the Human Brain Project (with contributions from the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Science Foundation). A.L. and M.H. were supported in part by an award from the Caltech Grubstakes program and Research Corporation Technologies, Tucson, AZ. M.H. was also supported by a fellowship from the Deutsche Forschungsgemeinschaft.",

year = "2000",

month = mar,

day = "1",

doi = "10.1038/73780",

language = "English (US)",

volume = "18",

pages = "321--325",

journal = "Nature biotechnology",

issn = "1087-0156",

publisher = "Nature Research",

number = "3",

}

TY - JOUR

T1 - In vivo visualization of gene expression using magnetic resonance imaging

AU - Louie, Angelique Y.

AU - Hüber, Martina M.

AU - Ahrens, Eric T.

AU - Rothbächer, Ute

AU - Moats, Rex

AU - Jacobs, Russell E.

AU - Fraser, Scott E.

AU - Meade, Thomas J.

N1 - Funding Information: The authors thank Chris Kintner for the pCS2+ cB-gal construct; C. LaBonne, R. Davis for the CS2P-nGFP construct; and Markus Friedrich for the pRc/RSV.ZL construct. This work was supported by the Biological Imaging Center of the Beckman Institute, National Institute of Health (AR42671), the National Institute of Child Health and Human Development, the National Center for Research Resources, and the Human Brain Project (with contributions from the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Science Foundation). A.L. and M.H. were supported in part by an award from the Caltech Grubstakes program and Research Corporation Technologies, Tucson, AZ. M.H. was also supported by a fellowship from the Deutsche Forschungsgemeinschaft.

PY - 2000/3/1

Y1 - 2000/3/1

N2 - 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.

AB - 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.

KW - Contrast agent

KW - Gadolinium

KW - Gene expression

KW - LacZ

KW - MRI

KW - β-galactosidase

UR - http://www.scopus.com/inward/record.url?scp=0342445413&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0342445413&partnerID=8YFLogxK

U2 - 10.1038/73780

DO - 10.1038/73780

M3 - Article

C2 - 10700150

AN - SCOPUS:0342445413

SN - 1087-0156

VL - 18

SP - 321

EP - 325

JO - Nature biotechnology

JF - Nature biotechnology

IS - 3

ER -

In vivo visualization of gene expression using magnetic resonance imaging

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this