Evaluation of 5-[123I] Iodo-arabino-uridine (123I-IaraU) as a Gene Probe for Tramp-C1/HSV1-sr39tk System

以Tramp-C1/HSV1-sr39tk系統探討碘－123標幟5-Iodo-arabino-uridine（碘－123-IaraU）作爲基因探針

孫偉倫(Wei-Lun Sun) ； 游靜芳(Ching-Fang Yu) ； 姜豐武(Li-Wu Chiang) ； 俞鍾山(Chung-Shan Yu) ； 江啓勳(Chi-Shiun Chiang) ； 李德偉(Te-Wei Lee) ； 羅建苗(Jem-Mau Lo)

《核子醫學雜誌》 22卷1期 (2009/03) Pp. 25-33

https://doi.org/10.6332/ANMS.2201.004

摘要

背景：5-Iodo-arabino-uridine (IaraU)爲較低細胞毒性之FIAU類化合物，可能較不適合作爲自殺基因治療藥物。本研究以腫瘤細胞及動物模型評估碘－123-IaraU作爲HSV1-sr39gtk報導基因系統造影探針之可行性。
方法：將HSV1-sr39tk基因與IL-3介蛋白轉殖於大鼠前列腺細胞株Tramp-C1，分別測試放射性碘標幟IaraU在此Tramp-C1/IL3-tk轉殖細胞株與原細胞株(Tramp-C1)之攝取率。分別將此兩種細胞株接種於C57BL/6J小鼠的左腹側與右腹側以產生腫瘤，其後以靜脈注射放射性碘標幟IaraU，注射後6小時及24小時分別執行生物分佈實驗。此小鼠在注射碘－123-IaraU後l小時、3小時、6小時及24小時進行micro SPECT/CT造影。
結果：生物分佈研究顯示注射後6小時大部分放射活度集中於腸胃道，注射後24小時則幾乎所有放射活度已排出體外。micro SPECT/CT造影顯示非常微量放射活度停留在植有Tramp-C1/IL3-tk的腫瘤，而植有Tramp-C1的腫瘤攝取則幾乎可忽略。
結論：本研究結果無法提供充分的證據顯示碘－123-IaraU在Tramp-C1/IL3-tk系統可作爲基因探針。

關鍵字

HSV-tk ； Tramp-C1 ； HSV1-sr39tk ； 碘－123-IaraU ； 基因探針

並列摘要

Background: 5-Iodo-arabino-uridine (IaraU) is a less toxic analogue of FIAU and may not be potential as a drug for suicide gene therapy. The purpose of this study was to evaluate the possibility of radioiodine labeled IaraU as a candidate for imaging HSV1-sr39tk report gene expression in tumor cells and animal model.
Methods: The rat prostate cancer cell line Tramp-C1 was transduced with HSV1-sr39tk and IL-3. Uptake of 123I-IaraU in the transduced Tramp-C1 referred as Tramp-C1/IL3-tk and in the parental Tramp-C1 as a control was tested. The Tramp-C1/IL3-tk cells as well as the Tramp-C1 cells were inoculated subcutaneously into the left flank and the right flank of C57BL/6J mice separately to produce the prostate tumor xenografts. Biodistribution study in the tumor-implanted animals was carried out after intravenous injection of 123I-IaraU at 6 h and 24 h. The animals were imaged by 123I-IaraU using micro SPECT/CT at 1, 3, 6, and 24 h postinjection.
Results: The biodistribution study showed intensive retention of the radioactivity in gastrointestinal tract at 6 h, and excreted almost exhaustively from the body at 24 h. The micro SPECT/CT imaging showed only trace uptake of 123I-IaraU in Tramp-C1/IL3-tk xenograft, and negligible uptake in the Tramp-C1 xenograft.
Conclusion: 123I-IaraU was deficiently evidenced as a probe to monitor gene expression in the Tramp-C1/HSV1-sr39tk system.

並列關鍵字

HSV1-tk ； Tramp-C1 ； HSV1-sr39tk ； 123I-IaraU ； gene probe