Dual <sup>19</sup>F/<sup>1</sup>H MR Gene Reporter
Molecules for <i>in Vivo</i> Detection of β-Galactosidase
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Abstract
Increased emphasis on personalized medicine and novel
therapies
requires the development of noninvasive strategies for assessing biochemistry <i>in vivo</i>. The detection of enzyme activity and gene expression <i>in vivo</i> 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 <sup>1</sup>H/<sup>19</sup>F nuclear magnetic
resonance (NMR) <i>lacZ</i> 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 <i>in vivo</i>. Substrates show a single <sup>19</sup>F NMR signal
and exposure to β-galactosidase induces a large <sup>19</sup>F NMR chemical shift response. In the presence of ferric ions, the
liberated aglycone generates intense proton MRI T<sub>2</sub> contrast.
The dual modality approach allows both the detection of substrate
and the imaging of product enhancing the confidence in enzyme detection