Dual 19F/ 1H MR gene reporter molecules for in vivo detection of β-galactosidase

Jian Xin Yu, Vikram D. Kodibagkar, Rami R. Hallac, Li Liu, Ralph P. Mason

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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 T 2 contrast. The dual modality approach allows both the detection of substrate and the imaging of product enhancing the confidence in enzyme detection.

Original languageEnglish (US)
Pages (from-to)596-603
Number of pages8
JournalBioconjugate Chemistry
Volume23
Issue number3
DOIs
StatePublished - Mar 21 2012

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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