Tumor-specific expression and detection of a CEST reporter gene

Magn Reson Med. 2015 Aug;74(2):544-9. doi: 10.1002/mrm.25748. Epub 2015 Apr 27.

Abstract

Purpose: To develop an imaging tool that enables the detection of malignant tissue with enhanced specificity using the exquisite spatial resolution of MRI.

Methods: Two mammalian gene expression vectors were created for the expression of the lysine-rich protein (LRP) under the control of the cytomegalovirus (CMV) promoter and the progression elevated gene-3 promoter (PEG-3 promoter) for constitutive and tumor-specific expression of LRP, respectively. Using those vectors, stable cell lines of rat 9L glioma, 9L(CMV-LRP) and 9L(PEG-LRP) , were established and tested for CEST contrast in vitro and in vivo.

Results: 9L(PEG-LRP) cells showed increased CEST contrast compared with 9L cells in vitro. Both 9L(CMV-LRP) and 9L(PEG-LRP) cells were capable of generating tumors in the brains of mice, with a similar growth rate to tumors derived from wild-type 9L cells. An increase in CEST contrast was clearly visible in tumors derived from both 9L(CMV-LRP) and 9L(PEG-LRP) cells at 3.4 ppm.

Conclusion: The PEG-3 promoter:LRP system can be used as a cancer-specific, molecular-genetic imaging reporter system in vivo. Because of the ubiquity of MR imaging in clinical practice, sensors of this class can be used to translate molecular-genetic imaging rapidly.

Keywords: PEG-3 promoter; chemical exchange saturation transfer; glioma; magnetic resonance imaging; molecular imaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics*
  • Female
  • Genes, Reporter / genetics*
  • Humans
  • Image Enhancement / methods
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mice
  • Molecular Imaging / methods*
  • Neoplasms, Experimental / genetics*
  • Neoplasms, Experimental / pathology*
  • Promoter Regions, Genetic / genetics
  • Rats
  • Reproducibility of Results
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor