title: MRI measurements of reporter-mediated increases in transmembrane water exchange enable detection of a gene reporter.
abstract: Non-invasive imaging of gene expression can be used to track implanted cells in vivo but often requires the addition of an exogenous contrast agent that may have limited tissue access. We show that the urea transporter (UT-B) can be used as a gene reporter, where reporter expression is detected using1H MRI measurements of UT-B-mediated increases in plasma membrane water exchange. HEK cells transfected with the reporter showed an increased apparent water exchange rate (AXR), which increased in line with UT-B expression. AXR values measured in vivo, in UT-B-expressing HEK cell xenografts, were significantly higher (about twofold, P < 0.0001), compared with non-expressing controls. Fluorescence imaging of a red fluorescent protein (mStrawberry), co-expressed with UT-B showed that UT-B expression correlated in a linear fashion with AXR. Transduction of rat brain cells in situ with a lentiviral vector expressing UT-B resulted in about a twofold increase in AXR at the site of virus injection.
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Franz
authors.initials: F
authors.lastname: Schilling
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Susana
authors.initials: S
authors.lastname: Ros
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
authors.forename: De-En
authors.initials: DE
authors.lastname: Hu
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Paula
authors.initials: P
authors.lastname: D'Santos
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: McGuire
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Mair
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Wright
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mannion
authors.affiliation: Wellcome Trust-Medical Research Council Stem Cell Institute and Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Robin J M
authors.initials: RJ
authors.lastname: Franklin
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
authors.forename: André A
authors.identifier: http://orcid.org/0000-0003-2740-5166
authors.initials: AA
authors.lastname: Neves
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.|Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brindle
mesh_terms: D000818:Animals; D001834:Body Water / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D005260:Female; D017930:Genes, Reporter / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D057054:Molecular Imaging / Q000379:methods; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000096982:Urea Transporters
chemical_list: D026901:Membrane Transport Proteins; D000096982:Urea Transporters