Potential of the FES-hERL PET reporter gene system -- basic evaluation for gene therapy monitoring

Nucl Med Biol. 2006 Jan;33(1):145-51. doi: 10.1016/j.nucmedbio.2005.07.013.

Abstract

Purpose: In vivo reporter genes can be powerful tools in supporting and ensuring the success of gene therapy. A careful and rational design of a reporter system is essential to realize a noninvasive in vivo reporter gene imaging system applicable for humans. We designed a new in vivo reporter gene imaging system that uses F-18-labeled estradiol (FES) and human estrogen receptor ligand (hERL) binding domain, taking advantage that FES is a radiopharmaceutical already being used for human studies with access to a wide range of tissues, including the brain, and that hERL lacking DNA binding domain can no longer work as a transcription factor, and carried out basic studies to evaluate its potential for gene therapy monitoring.

Methods: We constructed a plasmid (pTIER) to coexpress a model therapeutic gene and the reporter gene hERL and transfected Cos7 cells and examined their uptake of [(3)H]estradiol and FES in culture media. The uptake of FES by mouse calf muscle electroporated with pTIER was also tested.

Results: The cells transfected with pTIER took up the radioligands efficiently and specifically in culture media. Also, the mouse calf muscle electroporated with pTIER accumulated a higher amount of FES than did the control.

Conclusion: The data indicate that our new reporter gene system seems promising for in vivo imaging of gene expression and gene therapy monitoring.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Drug Evaluation, Preclinical
  • Estradiol / pharmacokinetics*
  • Feasibility Studies
  • Fluorine Radioisotopes / pharmacokinetics*
  • Genes, Reporter
  • Genetic Therapy / methods*
  • Humans
  • Mice
  • Positron-Emission Tomography / methods*
  • Prognosis
  • Radiopharmaceuticals / pharmacokinetics
  • Thymidine Phosphorylase / genetics*
  • Thymidine Phosphorylase / therapeutic use

Substances

  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Estradiol
  • Thymidine Phosphorylase