title: Dual-modality gene reporter for in vivo imaging.
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.
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
authors.forename: P Stephen
authors.initials: PS
authors.lastname: Patrick
authors.forename: Jayne
authors.initials: J
authors.lastname: Hammersley
authors.forename: Louiza
authors.initials: L
authors.lastname: Loizou
authors.forename: Mikko I
authors.initials: MI
authors.lastname: Kettunen
authors.forename: Tiago B
authors.initials: TB
authors.lastname: Rodrigues
authors.forename: De-En
authors.initials: DE
authors.lastname: Hu
authors.forename: Sui-Seng
authors.initials: SS
authors.lastname: Tee
authors.forename: Robin
authors.initials: R
authors.lastname: Hesketh
authors.forename: Scott K
authors.initials: SK
authors.lastname: Lyons
authors.forename: Dmitry
authors.initials: D
authors.lastname: Soloviev
authors.forename: David Y
authors.initials: DY
authors.lastname: Lewis
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Fulton
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brindle
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D005260:Female; D005682:Gadolinium / Q000737:chemistry; D019786:Gadolinium DTPA / Q000737:chemistry; D017930:Genes, Reporter; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007477:Ions; D061986:MCF-7 Cells; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence / Q000379:methods; D009368:Neoplasm Transplantation; D027361:Organic Anion Transporters / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D003287:Contrast Media; D007477:Ions; D027361:Organic Anion Transporters; C512988:SLCO1A2 protein, human; C073590:gadolinium ethoxybenzyl DTPA; D005682:Gadolinium; D019786:Gadolinium DTPA
keywords: Oatp; SPECT