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Basic Evaluation of FES-hERL PET Tracer-Reporter Gene System for In Vivo Monitoring of Adenoviral-Mediated Gene Therapy

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Abstract

Purpose

The purpose of the study is to evaluate the feasibility of human estrogen receptor α ligand binding domain (hERL) as a reporter gene in combination with positron emission tomography (PET) probe, 16α-[18F]fluoro-17β-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.

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Acknowledgements

We thank Mr. Shingo Kasamatsu, chief engineer of our center and Mr. Toshinao Nakakoji of CMI, Inc. for their excellent support during FES synthesis and professional operation of the cyclotron, respectively. We also thank Dr. Sakon Noriki and Mr. Kato, Department of Tumor Pathology, University of Fukui, for their kind guidance in immunohistochemistry. This work was partly supported by the 21st Century COE program “Biomedical Imaging Technology Integration Program” from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) Japan and a grant for the Collaboration of Regional Entities for the Advancement of technological excellence program “Regenerative Cell Therapy” from the Japan Science and Technology Agency.

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Authors and Affiliations

  1. Biomedical Imaging Research Center, University of Fukui, 23-3, Matsuoka- Shimoaizuki, Eiheiji-cho, Fukui, 910-1193, Japan

    Talakad Goolaiah Lohith, Takako Furukawa, Masato Kobayashi & Yasuhisa Fujibayashi

  2. Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan

    Tetsuya Mori

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  1. Talakad Goolaiah Lohith
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  2. Takako Furukawa
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  3. Tetsuya Mori
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  4. Masato Kobayashi
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  5. Yasuhisa Fujibayashi
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Corresponding author

Correspondence to Yasuhisa Fujibayashi.

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Lohith, T.G., Furukawa, T., Mori, T. et al. Basic Evaluation of FES-hERL PET Tracer-Reporter Gene System for In Vivo Monitoring of Adenoviral-Mediated Gene Therapy. Mol Imaging Biol 10, 245–252 (2008). https://doi.org/10.1007/s11307-008-0149-0

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  • DOI: https://doi.org/10.1007/s11307-008-0149-0

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