MRI measurements of reporter-mediated increases in transmembrane water exchange enable detection of a gene reporter

• Published in: Nature biotechnology Vol. 35; no. 1; pp. 75 - 80
• Main Authors: Schilling, Franz, Ros, Susana, Hu, De-En, D'Santos, Paula, McGuire, Sarah, Mair, Richard, Wright, Alan J, Mannion, Elizabeth, Franklin, Robin J M, Neves, André A, Brindle, Kevin M
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-01-2017; Nature Publishing Group
• Subjects: 631/1647/245/1628; 631/61/2296; Agriculture; Animals; Bioinformatics; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Body Water - metabolism; Cell division; Cell Membrane - metabolism; Contrast agents; Female; Gene expression; Genes, Reporter - genetics; HEK293 Cells; Humans; letter; Life Sciences; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Membranes (Biology); Methods; Molecular Imaging - methods; Physiological aspects; Protein expression; Proteins; Proton Magnetic Resonance Spectroscopy - methods; Rats; Reproducibility of Results; Sensitivity and Specificity; Spectrum analysis; Urea; Urea Transporters; Water exchange; United Kingdom > UK
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt.3714

Urea transporter can be used as a sensitive, contrast agent-free gene reporter for magnetic resonance imaging in cells and whole animals.
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
1
. We show that the urea transporter (UT-B) can be used as a gene reporter, where reporter expression is detected using
1
H 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.