Serial In Vivo imaging og the Lung Metastases Model and Gene Therapy Using HSV1-tk and Ganciclovir

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题名:	Serial In Vivo imaging og the Lung Metastases Model and Gene Therapy Using HSV1-tk and Ganciclovir
作者:	(Win-Ping Deng);(Cheng-Chia Wu);(Chien-Chih Lee);楊文光(Wen-Kuang Yang);(Hsin-Ell Wang);(Ren-Shyan Liu);(Hon-Jian Wei);(Juri G. Gelovani);(Jeng-Jong Hwang);(Den-Mei Yang);(Fu YK);(Wu CW)*
贡献者:	醫學院臨床醫學研究所;中國附醫醫學研究部細胞及基因治療研究室
日期:	2006-05
上传时间:	2009-08-26 16:13:39 (UTC+8)
摘要:	Noninvasive imaging in lung metastatic tumor models is used infrequently because of technical limitations in detecting metastases. We have previously used 29-fluoro-29-deoxy-5-iodo- 1-b-D-arabinofuranosyluracil labeled with 131I (131I-FIAU) and demonstrated the applicability of noninvasive imaging for monitoring cancer gene therapy in an experimental animalmodel of herpes simplex virus type 1 thymidine kinase (HSV1-tk)–expressing tumor xenografts.We have nowusedthe same animalmodel to effectively and noninvasively monitor the location,magnitude, and duration of therapeutic gene expression over time for the lung metastases model. Methods: To improve the detectability of lung metastases, an experimental blood-borne lung metastases model in mice was established using intravenously administered HSV1-tk–expressing NG4TL4 fibrosarcoma cells (NG4TL4-TK) and simulated the clinical application of HSV1-tk plus ganciclovir (GCV) prodrug activation gene therapy. The efficacy of noninvasively monitoring the sites of development of lung metastatic lesions and their GCV-induced regression were assessed by SPECT with 131I-FIAU. Results: The results of this study showed that the lung metastases model of NG4TL4-TK cells could be successfully detected as early as 24 h after intravenous injection of tumor cells radiolabeled with 131IFIAU and also subsequently detected by extended monitoring with the intravenous injection of 131I-FIAUon day 10. Inmice treated with GCV, g-camera imaging demonstrated a significant growth inhibition of NG4TL4-TK cells of primary tumors and lung metastases on day 7 after initiating treatment. Conclusion: We conclude that this in vivo imaging approach will be useful for future studies of the lung metastases model and for the assessment of novel anticancer and antimetastatic therapies.
關聯:	JOURNAL OF NUCLEAR MEDICINE 47(5 )877 ~884
显示于类别:	[臨床醫學研究所] 期刊論文

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