Basic evaluation of FES-hERL PET tracer-reporter gene system for in vivo monitoring of adenoviral-mediated gene therapy

Mol Imaging Biol. 2008 Sep;10(5):245-52. doi: 10.1007/s11307-008-0149-0. Epub 2008 Jun 12.

Abstract

Purpose: The purpose of the study is to evaluate the feasibility of human estrogen receptor alpha ligand binding domain (hERL) as a reporter gene in combination with positron emission tomography (PET) probe, 16alpha-[18F]fluoro-17beta-estradiol (FES), in an adenovirus gene delivery system.

Methods: An adenoviral vector (test), carrying hERL gene and a model angiogenesis therapeutic gene (human thymidine phosphorylase, hTP) was constructed along with a control vector. In vitro radioligand binding and expression studies were performed on various cell lines. The control and test viruses were injected into contralateral adductor muscles of a rat followed by FES-PET imaging and immunohistochemical staining of resected muscle samples.

Results: A high FES uptake accompanied by hERL and hTP expression was obtained both in vitro and in vivo by the test adenovirus infection.

Conclusion: Considering the versatile tissue permeability of the probe, highly efficient gene expression, and safeness for human use, we expect our reporter gene system to have favorable characteristics for clinical application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Cell Line
  • Cell Lineage
  • Chlorocebus aethiops
  • Estradiol / analogs & derivatives*
  • Estradiol / metabolism
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism*
  • Gene Expression / genetics
  • Genes, Reporter / genetics*
  • Genetic Therapy / methods*
  • Humans
  • Ligands
  • Positron-Emission Tomography / methods*
  • Rats

Substances

  • Estrogen Receptor alpha
  • Ligands
  • Estradiol
  • 16-fluoroestradiol