Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu 300, Taiwan.
Nucl Med Biol. 2012 Apr;39(3):371-6. doi: 10.1016/j.nucmedbio.2011.09.003. Epub 2011 Nov 29.
As one of the most intensively studied probes for imaging of the cellular proliferation, [(18)F]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-[(123)I]Iodo arabinosyl uridine ([(123)I]IaraU) was prepared in a radiochemical yield of 8% and specific activity of 21 GBq/μmol, 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'-fluoro-5-iodo arabinosyl uridine (FIAU). Due to potential instability of the iodo group, accumulation index of 1.6 for [(123)I]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 [(18)F]FLT at 5 h. The results from competitive inhibition by these nucleosides against the accumulation of [(18)F]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 [(18)F]FLT and HSV1-TK provides a synergistic imaging potency.
作为细胞增殖成像研究最深入的探针之一，研究了胸苷激酶 1（TK1）依赖性的靶向特异性是否可以通过单纯疱疹病毒 1 型（HSV1）tk 基因介导的协同作用增强，具体表现在 TK1 或 TK2 的表达上。5-[[123I]碘代]阿拉伯呋喃糖尿嘧啶([(123)I]IaraU)的放射化学产率分别为 8%和 21GBq/μmol，比活度分别为 21GBq/μmol。通过使用阿拉伯呋喃糖尿嘧啶类似物（如 5-碘、5-氟和 5-(E)-碘代乙烯基阿拉伯呋喃糖尿嘧啶）以及 2'-氟-5-碘代阿拉伯呋喃糖尿嘧啶（FIAU）比较这两种示踪剂的细胞摄取抑制。由于碘基团的潜在不稳定性，HSV1-TK 对 [(123)I]IaraU 的积聚指数在 1.5 小时时几乎可以达到 1.6，但在 5 小时时与 [(18)F]FLT 的 2.0 相比下降到 0.2。这些核苷对 [(18)F]FLT 积累的竞争性抑制的结果表明，FLT 由于胸苷激酶状态的转变，对 HSV1-tk 基因转染表现出混合的 TK1 和 TK2 依赖性抑制。总之，[(18)F]FLT 和 HSV1-TK 的结合提供了协同的成像效力。
