Dual-modality gene reporter for in vivo imaging

Patrick, P. S., Hammersley, J., Loizou, L., Kettunen, M. I., Rodrigues, T. B., Hu, D. E., Tee, S. S., Hesketh, R., Lyons, S. K., Soloviev, D., Lewis, D. Y., Aime, S., Fulton, S. M., Brindle, K. M. (January 2014) Dual-modality gene reporter for in vivo imaging. Proc Natl Acad Sci U S A, 111 (1). pp. 415-20. ISSN 1091-6490 (Electronic)0027-8424 (Linking)

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Abstract

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, Gd(3+)-based, hepatotrophic contrast agent (gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid). Cells expressing the reporter showed readily reversible, intense, and positive contrast (up to 7.8-fold signal enhancement) in T1-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 Gd(3+) ion for the radionuclide, (111)In, also allowed detection by single-photon emission computed tomography, thus combining the spatial resolution of MRI with the sensitivity of radionuclide imaging.

Item Type: Paper
Uncontrolled Keywords: Animals Cell Line, Tumor Contrast Media/chemistry Female Gadolinium/chemistry Gadolinium DTPA/chemistry *Genes, Reporter HCT116 Cells HEK293 Cells Humans Image Enhancement/methods Ions MCF-7 Cells Magnetic Resonance Imaging/*methods Mice Mice, SCID Microscopy, Fluorescence/methods Neoplasm Transplantation Organic Anion Transporters/metabolism Tomography, Emission-Computed, Single-Photon/methods Oatp Spect
Subjects: Investigative techniques and equipment > imaging
CSHL Authors:
Communities: CSHL labs > Lyons lab
Depositing User: Matt Covey
Date: 7 January 2014
Date Deposited: 11 May 2017 20:26
Last Modified: 08 Nov 2017 20:40
PMCID: PMC3890795
Related URLs:
URI: https://repository.cshl.edu/id/eprint/34725

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