Potential of the FES–hERL PET reporter gene system — Basic evaluation for gene therapy monitoring

• Published in: Nuclear medicine and biology 2006, Vol.33 (1), p.145-151
• Main Authors: Furukawa, Takako, Lohith, Talakad G., Takamatsu, Shinji, Mori, Tetsuya, Tanaka, Takeshi, Fujibayashi, Yasuhisa
• Format: Article
• Language: English
• Subjects: Animals; Cercopithecus aethiops; COS Cells; Drug Evaluation, Preclinical; Estradiol - pharmacokinetics; Estrogen receptor; Feasibility Studies; Fluorine Radioisotopes - pharmacokinetics; Fluoroestradiol; Gene therapy; Genes, Reporter; Genetic Therapy - methods; Humans; Mice; Positron emission tomography; Positron-Emission Tomography - methods; Prognosis; Radiopharmaceuticals - pharmacokinetics; Reporter gene; Thymidine Phosphorylase - genetics; Thymidine Phosphorylase - therapeutic use
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2005.07.013

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. 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 [ 3H]estradiol and FES in culture media. The uptake of FES by mouse calf muscle electroporated with pTIER was also tested. 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. The data indicate that our new reporter gene system seems promising for in vivo imaging of gene expression and gene therapy monitoring.