Increased emphasis on personalized medicine and novel therapies requires the development of noninvasive strategies for assessing biochemistry in vivo. The detection of enzyme activity and gene expression in vivo is potentially important for the characterization of diseases and gene therapy. Magnetic resonance imaging (MRI) is a particularly promising tool, since it is noninvasive and has no associated radioactivity, yet penetrates deep tissue. We now demonstrate a novel class of dual 1H/19F nuclear magnetic resonance (NMR) lacZ gene reporter molecule to specifically reveal enzyme activity in human tumor xenografts growing in mice. We report the design, synthesis, and characterization of six novel molecules and evaluation of the most effective reporter in mice in vivo. Substrates show a single 19F NMR signal and exposure to β-galactosidase induces a large 19F NMR chemical shift response. In the presence of ferric ions, the liberated aglycone generates intense proton MRI T2 contrast. The dual modality approach allows both the detection of substrate and the imaging of product enhancing the confidence in enzyme detection.
|Original language||English (US)|
|Number of pages||8|
|State||Published - Mar 21 2012|
ASJC Scopus subject areas
- Biomedical Engineering
- Pharmaceutical Science
- Organic Chemistry