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In vivo visualization of gene expression using magnetic resonance imaging

Louie, Angelique Y. and Hüber, Martina M. and Ahrens, Eric T. and Rothbächer, Ute and Moats, Rex and Jacobs, Russell E. and Fraser, Scott E. and Meade, Thomas J. (2000) In vivo visualization of gene expression using magnetic resonance imaging. Nature Biotechnology, 18 (3). pp. 321-325. ISSN 1087-0156. https://resolver.caltech.edu/CaltechAUTHORS:20150407-142052616

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/73780DOIArticle
http://www.nature.com/nbt/journal/v18/n3/full/nbt0300_321.htmlPublisherArticle
ORCID:
AuthorORCID
Jacobs, Russell E.0000-0002-1382-8486
Fraser, Scott E.0000-0002-5377-0223
Additional Information:© 2000 Nature America Inc. Received 4 November 1999; accepted 29 December 1999. 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.
Funders:
Funding AgencyGrant Number
Beckman Institute Biological Imaging CenterUNSPECIFIED
NIHAR42671
National Institute of Child Health and Human DevelopmentUNSPECIFIED
National Center for Research ResourcesUNSPECIFIED
Human Brain ProjectUNSPECIFIED
National Institute on Drug AbuseUNSPECIFIED
National Institute of Mental Health (NIMH)UNSPECIFIED
NSFUNSPECIFIED
Caltech Grubstake FundUNSPECIFIED
Research Corporation TechnologiesUNSPECIFIED
Deutsche Forschungsgemeinschaft (DFG)UNSPECIFIED
Subject Keywords:MRI, gene expression, contrast agent, b-galactosidase, gadolinium, lacZ, MRI
Issue or Number:3
Record Number:CaltechAUTHORS:20150407-142052616
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150407-142052616
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:56442
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:07 Apr 2015 22:10
Last Modified:03 Oct 2019 08:13

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