核子醫學分子造影於基因治療之應用

Non-Invasive Mapping of Gene Expression for Gene Therapy with Molecular Nuclear Medicine Imaging

10.6332/ANMS.1404.012

鄧文炳(Win-Ping Deng)；張志賢(Chih-Hsien Chang)；賴文福(Wen-Fu Lai)；王信二(Hsin-Ell Wang)；丁幹(Gann Ting)；楊文光(Wen K. Yang)；劉仁賢(Ren-Shyan Liu)

非侵入性 ； 核子醫學造影 ； 癌症治療 ； 基因治療 ； 正子電腦斷層掃描 ； 單光子電腦斷層掃描 ； non-invasive ； nuclear medicine imaging ； cancer therapy ； gene therapy ； PET ； SPECT ； herpes simplex virus ； thymidine kinase ； marker substrate ； marker gene ； reporter gene

核子醫學雜誌

14卷4期（2001 / 12 / 01）

237 - 246

繁體中文

分子生物及分子遺傳技術突飛猛進，對於人類的疾病，特別是惡性腫瘤「癌症」希望能找出有效的治療方式，基因治療便是其中之一。惡性腫瘤的基因治療在臨床應用前，下列幾個問題必須獲得解答：基因在體內是否轉植成功？是否表現？是否表現在標的器官（target organ）或標的組織（target tissue）？表現是否適量？何時會表現到最大量？何時是治療用藥最合適的時刻？表現時間多長？是否達到治療效果？理論上，非侵入性核醫分子造影可以回答以上的各項問題，其方法是在植入基因中加入一段「指標基因（marker gene）」，再配合使用其相對的「指標受質（marker substrate）」，藉由非侵入性核醫分子造影，在不同時間監測含有放射性同位素標幟之「指標受質」在體內分佈與代謝；如此，藉由動力學的測量（kinetic measurements），可以分析轉植基因在體內表現最為適當的時間、數量及生物分佈，同時病人不需接受侵入性組織切片檢查之痛苦與風險。本文回顧全世界運用核醫分子造影，並追蹤基因產物在體內表現的時間及數量，以確認基因治療效果等有關研究之現況與未來之展望。

The increasing knowledge of the molecular biology and molecular genetics of human diseases, particularly in human cancer, has led to the application of new biological therapeutic approaches such as gene-based therapy. A limitation of many gene-based therapies has been the inability to achieve controlled and effective delivery of gene to the target cells or tissues. In addition, several issues that are important for clinical optimization of gene therapy remain unresolved: (a) whether gene transduction has been successful; (b) what is the distribution of transduced target cells; (c) whether the level of gene expression is adequate. A noninvasive, clinically applicable method for imaging gene transduction in target tissue or specific organs of the body, thus assessing the kinetic changes of functional expression of the therapeutic gene, would be of considerable value. This paper reviewed and discussed the successful clinical application of this method to monitor gene expression which will require the appropriate combination of marker gene and marker substrate. This will facilitate the monitoring and evaluation of gene therapy in human subjects by defining the location, magnitude, and persistence of gene expression over time.