Journal
BIOCONJUGATE CHEMISTRY
Volume 23, Issue 3, Pages 596-603Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bc200647q
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Funding
- NCI [R21 CA120774, U24 CA126608, P30 CA142543]
- DOD Breast Cancer Initiative IDEA [DAMD17-031-0343]
- Small Animal Imaging Research Program
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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 H-1/F-19 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 F-19 NMR signal and exposure to beta-galactosidase induces a large F-19 NMR chemical shift response. In the presence of ferric ions, the liberated aglycone generates intense proton MRI T-2 contrast. The dual modality approach allows both the detection of substrate and the imaging of product enhancing the confidence in enzyme detection.
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