Study of [¹⁸F]FLT and [¹²³I]IaraU for cellular imaging in HSV1 tk-transfected murine fibrosarcoma cells: evaluation of the tracer uptake using 5-fluoro, 5-iodo and 5-iodovinyl arabinosyl uridines as competitive probes

详细信息	查看全文 | 推荐本文 |

• 作者：Ho-Lien Huang^a ; Li-Wu Chiang^a ; Jia-Rong Chen^a ; Wen K. Yang^b ; ^c ; Kee-Ching Jeng^d ; Jenn-Tzong Chen^e ; Ting-Shien Duh^e ; Wuu-Jyh Lin^e ; Shiou-Shiow Farn^a ; ^e ; Chi-Shiun Chiang^a ; Chia-Wen Huang^a ; Kun-I Lin^a ; ^f ; Chung-Shan Yu^a ; ^g ; ^{csyu@mx.nthu.edu.tw}
• 关键词：HSV1 tk ; Arabinosyl uridine ; TK2 ; Synergistic ; Inhibition
• 刊名：Nuclear Medicine and Biology
• 出版年：2012
• 期刊代码：43_09698051
• 类别：ph
• 出版时间：April, 2012
• 卷：39
• 期：3
• 页码：371-376
• 文件大小：358 K

摘要

As one of the most intensively studied probes for imaging of the cellular proliferation, [¹⁸F]FLT was investigated whether the targeting specificity of thymidine kinase 1 (TK1) dependency could be enhanced through a synergistic effect mediated by herpes simplex type 1 virus (HSV1) tk gene in terms of the TK1 or TK2 expression. 5-[¹²³I]Iodo arabinosyl uridine ([¹²³I]IaraU) was prepared in a radiochemical yield of 8%and specific activity of 21 GBq/渭mol, respectively. Inhibition of the cellular uptake of these two tracers was compared by using the arabinosyl uridine analogs such as 5-iodo, 5-fluoro and 5-(E)-iodovinyl arabinosyl uridine along with 2鈥?fluoro-5-iodo arabinosyl uridine (FIAU). Due to potential instability of the iodo group, accumulation index of 1.6 for [¹²³I]IaraU by HSV1-TK vs. control cells could virtually be achieved at 1.5 h, but dropped to 0.2 compared to 2.0 for [¹⁸F]FLT at 5 h. The results from competitive inhibition by these nucleosides against the accumulation of [¹⁸F]FLT implied that FLT exerted a mixed TK1- and TK2-dependent inhibition with HSV1-tk gene transfection because of the shifting of thymidine kinase status. Taken together, the combination of [¹⁸F]FLT and HSV1-TK provides a synergistic imaging potency.