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


CONCLUSIONS
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.
Lohith
Talakad Goolaiah
TG
Biomedical Imaging Research Center, University of Fukui, 23-3, Matsuoka- Shimoaizuki, Eiheiji-cho, Fukui 910-1193, Japan.
Furukawa
Takako
T
Mori
Tetsuya
T
Kobayashi
Masato
M
Fujibayashi
Yasuhisa
Y
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D019070:Cell Lineage; D002522:Chlorocebus aethiops; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008024:Ligands; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats
D047628:Estrogen Receptor alpha; D008024:Ligands; D004958:Estradiol; C043436:16-fluoroestradiol