Imaging of Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression with Radiolabeled 5-(2-iodovinyl)-2'-deoxyuridine (IVDU) in Liver by Hydrodynamic-based Procedure.
- Author:
Inho SONG
1
;
Tae Sup LEE
;
Joo Hyun KANG
;
Yong Jin LEE
;
Kwang Il KIM
;
Gwang Il AN
;
Wee Sup CHUNG
;
Gi Jeong CHEON
;
Chang Woon CHOI
;
Sang Moo LIM
Author Information
1. Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea. kang2325@kirams.re.kr
- Publication Type:Original Article
- Keywords:
Hydrodynamic-based procedure;
HSV1-tk;
IVDU;
liver;
molecular imaging
- MeSH:
Animals;
Autoradiography;
DNA;
Fluorescence;
Gene Expression;
Genes, Reporter;
Herpes Simplex;
Herpesvirus 1, Human;
Idoxuridine;
Liver;
Methylmethacrylates;
Mice;
Molecular Imaging;
Optical Imaging;
Plasmids;
Polystyrenes;
RNA, Messenger;
Simplexvirus;
Thymidine Kinase
- From:Nuclear Medicine and Molecular Imaging
2009;43(5):468-477
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Hydrodynamic-based procedure is a simple and effective gene delivery method to lead a high gene expression in liver tissue. Non-invasive imaging reporter gene system has been used widely with herpes simplex virus type 1 thymidine kinase (HSV1-tk) and its various substrates. In the present study, we investigated to image the expression of HSV1-tk gene with 5-(2-iodovinyl)-2'-deoxyuridine (IVDU) in mouse liver by the hydrodynamicbased procedure. MATERIALS AND METHODS: HSV1-tk or enhanced green fluorescence protein (EGFP) encoded plasmid DNA was transferred into the mouse liver by hydrodynaminc injection. At 24 h post-injection, RT-PCR, biodistribution, fluorescence imaging, nuclear imaging and digital wholebody autoradiography (DWBA) were performed to confirm transferred gene expression. RESULTS: In RT-PCR assay using mRNA from the mouse liver, specific bands of HSV1-tk and EGFP gene were observed in HSV1-tk and EGFP expressing plasmid injected mouse, respectively. Higher uptake of radiolabeled IVDU was exhibited in liver of HSV1-tk gene transferred mouse by biodistribution study. In fluorescence imaging, the liver showed specific fluorescence signal in EGFP gene transferred mouse. Gamma-camera image and DWBA results showed that radiolabeled IVDU was accumulated in the liver of HSV1-tk gene transferred mouse. CONCLUSION: In this study, hydrodynamic-based procedure was effective in liver-specific gene delivery and it could be quantified with molecular imaging methods. Therefore, co-expression of HSV1-tk reporter gene and target gene by hydrodynamic-based procedure is expected to be a useful method for the evaluation of the target gene expression level with radiolabeled IVDU.
