Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 1, Pages 415-420Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1319000111
Keywords
SPECT; Oatp
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Funding
- Medical Research Council and Cancer Research UK (CRUK)
- Biotechnology and Biological Sciences Research Council studentship
- University of Cambridge Overseas Research Studentship
- Yousef Jameel studentship
- European Commission
- Intra-European Marie Curie
- Long-Term European Molecular Biology Organization [EMBO-ALT-1145-2009]
- CRUK
- Cancer Research UK [16465, 17242] Funding Source: researchfish
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The ability to track cells and their patterns of gene expression in living organisms can increase our understanding of tissue development and disease. Gene reporters for bioluminescence, fluorescence, radionuclide, and magnetic resonance imaging (MRI) have been described but these suffer variously from limited depth penetration, spatial resolution, and sensitivity. We describe here a gene reporter, based on the organic anion transporting protein Oatp1a1, which mediates uptake of a clinically approved, Gd3+-based, hepatotrophic contrast agent (gadolinium-ethoxybenzyldiethylenetriamine pentaacetic acid). Cells expressing the reporter showed readily reversible, intense, and positive contrast (up to 7.8-fold signal enhancement) in T-1-weighted magnetic resonance images acquired in vivo. The maximum signal enhancement obtained so far is more than double that produced by MRI gene reporters described previously. Exchanging the Gd3+ ion for the radionuclide, In-111, also allowed detection by single-photon emission computed tomography, thus combining the spatial resolution of MRI with the sensitivity of radionuclide imaging.
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