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Na/I Symporter (NIS) Reporter Gene Imaging System for Evaluating Angiogenic Gene Therapy Using Hepatocyte Growth Factor
https://repo.qst.go.jp/records/69456
https://repo.qst.go.jp/records/69456fb7361e4-d0f6-42b1-a2e3-14fe4e6202c5
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2008-09-18 | |||||
| タイトル | ||||||
| タイトル | Na/I Symporter (NIS) Reporter Gene Imaging System for Evaluating Angiogenic Gene Therapy Using Hepatocyte Growth Factor | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Inubushi, Masayuki
× Inubushi, Masayuki× 犬伏 正幸 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Purpose: Hepatocyte growth factor (HGF) is a unique factor with strong angiogenic and antifibrotic effects, and thus is a promising candidate for an effective therapeutic gene in angiogenic gene therapy for ischemic heart disease. In this study, we aimed at constructing and in vitro validating a coexpression vector of a HGF therapeutic gene and an Na/I symporter (NIS) radionuclide reporter gene, and at in vivo imaging the transferred gene expression in a rat myocardial infarct model. Method: Adenovirus expressing HGF and NIS individually driven by two cytomegalovirus promoters (Ad-CMV-HGF-CMV-NIS) was constructed. In in-vitro experiments, western blotting analysis and Tc-99m pertechnetate uptake rate measurement were performed after infecting Ad-CMV-HGF-CMV-NIS with rat embryonic cardiomyoblast cells (H9c2) in various multiplicity of infection (MOI=0, 1, 5, 10, 20, 50, 100). For in-vivo imaging, Ad-CMV-HGF-CMV-NIS was injected through a thoracotomy directly into the left ventricular myocardium of peri-infarct areas immediately after ligating the left anterior descending (LAD) coronary artery. Three to five days later, expression of the transferred genes was imaged with Tc-99m pertechnetate using a small animal PET/SPECT/CT scanner (Siemens Inveon), also myocardial blood flow with Tc-99m tetrofosmin, and glucose metabolism with F-18 FDG. Results: The western blotting analysis demonstrated the amount of HGF and NIS proteins increased according to MOI and significantly correlated each other (r=0.93). Tc-99m pertechnetate uptake rate increased according to MOI up to 582 times higher than non-infected control, and was blocked by KClO4. In Tc-99m pertechnetate SPECT imaging, the transferred gene expression was clearly visualized as focal tracer accumulation, and its location was prehensible in reference to areas with hypoperfusion or metabolic disorder on fusion images with Tetrofosmin-SPECT or FDG-PET. Conclusion: The NIS reporter gene imaging system offers the potential of evaluating the usefulness of HGF angiogenic gene therapy based on non-invasive monitoring of the therapeutic gene expression. | |||||
| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | World Molecular Imaging Congress | |||||
| 発表年月日 | ||||||
| 日付 | 2008-09-13 | |||||
| 日付タイプ | Issued | |||||
