Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan.
Nucl Med Biol. 2011 Oct;38(7):987-95. doi: 10.1016/j.nucmedbio.2011.04.003. Epub 2011 Jun 22.
Herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene in combination with radiolabeled nucleoside substrates is the most widely used reporter system. This study characterized 1-(2'-deoxy-2'-[(18)F]fluoro-β-D-arabinofuranosyl)-5-iodocytosine ((18)F-FIAC) as a new potential positron emission tomography (PET) probe for HSV1-tk gene imaging and compared it with 2'-deoxy-2'-[(18)F]fluoro-5-iodo-1-β-D-arabinofuranosyluracil ((18)F-FIAU) and 2'-deoxy-2'-[(18)F]fluoro-5-ethyl-1-β-D-arabinofuranosyluracil((18)F-FEAU) (thymidine analogues) in an NG4TL4-WT/STK sarcoma-bearing mouse model.
A cellular uptake assay, biodistribution study, radioactive metabolites assay and microPET imaging of NG4TL4-WT/STK tumor-bearing mice post administration of (18)F-FIAC, (18)F-FIAU and (18)F-FEAU were conducted to characterize the biological properties of these tracers.
Highly specific uptake of (18)F-FIAC, (18)F-FIAU and (18)F-FEAU in tk-transfected [tk(+)] cells was observed. The tk(+)-to-tk(-) cellular uptake ratio after a 2-h incubation was 66.6±25.1, 76.3±18.2 and 247.2±37.2, respectively. In biodistribution studies, (18)F-FIAC showed significant tk(+) tumor specificity (12.6; expressed as the tk(+)-to-tk(-) tumor uptake ratio at 2 h postinjection) comparable with (18)F-FIAU (15.8) but lower than (18)F-FEAU (48.0). The results of microPET imaging also revealed the highly specific accumulation of these three radioprobes in the NG4TL4-tk(+) tumor.
Our findings suggested that the cytidine analogue (18)F-FIAC is a new potential PET probe for the imaging of HSV1-tk gene expression. (18)F-FIAC may be regarded as the prodrug of (18)F-FIAU in vivo.
单纯疱疹病毒 1 胸苷激酶（HSV1-tk）基因与放射性标记核苷底物结合是应用最广泛的报告系统。本研究将 1-（2'-脱氧-2'-[（18）F]氟-β-D-阿拉伯呋喃糖基）-5-碘胞嘧啶（（18）F-FIAC）作为一种新的正电子发射断层扫描（PET）探针用于 HSV1-tk 基因成像，并与 2'-脱氧-2'-[（18）F]氟-5-碘-1-β-D-阿拉伯呋喃尿嘧啶（（18）F-FIAU）和 2'-脱氧-2'-[（18）F]氟-5-乙基-1-β-D-阿拉伯呋喃尿嘧啶（（18）F-FEAU）（胸苷类似物）进行比较，这些探针在 NG4TL4-WT/STK 肉瘤荷瘤小鼠模型中进行了细胞摄取分析、生物分布研究、放射性代谢产物分析和 microPET 成像。
进行了细胞摄取分析、生物分布研究、放射性代谢产物分析和 microPET 成像，以研究 NG4TL4-WT/STK 肿瘤荷瘤小鼠给药后（18）F-FIAC、（18）F-FIAU 和（18）F-FEAU 的生物特性。
在 tk 转染的[tk(+)]细胞中观察到（18）F-FIAC、（18）F-FIAU 和（18）F-FEAU 的高度特异性摄取。孵育 2 小时后，tk(+)-to-tk(-)细胞摄取比值分别为 66.6±25.1、76.3±18.2 和 247.2±37.2。在生物分布研究中，（18）F-FIAC 显示出与（18）F-FIAU（15.8）相当的显著 tk(+)肿瘤特异性（注射后 2 小时 tk(+)-to-tk(-)肿瘤摄取比值为 12.6），但低于（18）F-FEAU（48.0）。microPET 成像结果也显示这三种放射性探针在 NG4TL4-tk(+)肿瘤中的高度特异性积累。
我们的研究结果表明，胞嘧啶类似物（18）F-FIAC 是一种用于 HSV1-tk 基因表达成像的新型潜在 PET 探针。（18）F-FIAC 可能是体内（18）F-FIAU 的前体药物。
