Karmanos Cancer Institute, Wayne State University, 4100 John R, 4 HWCRC, Detroit, MI 48201-2013, USA.
Eur J Nucl Med Mol Imaging. 2009 Dec;36(12):1987-93. doi: 10.1007/s00259-009-1177-y.
FIAU, (1-(2'-deoxy-2'-fluoro-1-β-D-arabinofuranosyl)-5-iodouracil) has been used as a substrate for herpes simplex virus thymidine kinases (HSV-TK and HSV-tk, for protein and gene expression, respectively) and other bacterial and viral thymidine kinases for noninvasive imaging applications. Previous studies have reported the formation of a de-iodinated metabolite of 18F-FIAU. This study reports the dynamic tumor uptake, biodistribution, and metabolite contribution to the activity of 18F-FIAU seen in HSV-tk gene expressing tumors and compares the distribution properties with its de-iodinated metabolite 18F-FAU.
CD-1 nu/nu mice with subcutaneous MH3924A and MH3924A-stb-tk+ xenografts on opposite flanks were used for the biodistribution and imaging studies. Mice were injected IV with either 18F-FIAU or 18F-FAU. Mice underwent dynamic imaging with each tracer for 65 min followed by additional static imaging up to 150 min post-injection for some animals. Animals were sacrificed at 60 or 150 min post-injection. Samples of blood and tissue were collected for biodistribution and metabolite analysis. Regions of interest were drawn over the images obtained from both tumors to calculate the time-activity curves.
Biodistribution and imaging studies showed the highest uptake of 18F-FIAU in the MH3924A-stb-tk+ tumors. Dynamic imaging studies revealed a continuous accumulation of 18F-FIAU in HSV-TK expressing tumors over 60 min. The mean biodistribution values (SUV ± SE) for MH3924A-stb-tk+ were 2.07 ± 0.40 and 6.15 ± 1.58 and that of MH3924A tumors were 0.19 ± 0.07 and 0.47 ± 0.06 at 60 and 150 min, respectively. In 18F-FIAU injected mice, at 60 min nearly 63% of blood activity was present as its metabolite 18F-FAU. Imaging and biodistribution studies with 18F-FAU demonstrated no specific accumulation in MH3924A-stb-tk+ tumors and SUVs for both the tumors were similar to those observed with muscle.
18F-FIAU shows a continuous accumulation of activity in HSV-TK expressing tumors. 18F-FAU does not show any preferential accumulation in HSV-TK expressing tumors. In the 18F-FIAU treated mice, the 18F-FAU contribution to the total uptake seen in HSV-TK positive tumors is minimal.
FIAU（1-（2'-脱氧-2'-氟-1-β-D-阿拉伯呋喃糖基）-5-碘尿嘧啶）已被用作单纯疱疹病毒胸苷激酶（HSV-TK 和 HSV-tk，分别用于蛋白和基因表达）和其他细菌和病毒胸苷激酶的底物，用于非侵入性成像应用。以前的研究报告了 18F-FIAU 的脱碘代谢物的形成。本研究报告了 HSV-tk 基因表达肿瘤中观察到的 18F-FIAU 的动态肿瘤摄取、生物分布和代谢产物对其活性的贡献，并将其分布特性与其脱碘代谢产物 18F-FAU 进行了比较。
使用 CD-1 nu/nu 小鼠，在其两侧皮下接种 MH3924A 和 MH3924A-stb-tk+异种移植物，用于生物分布和成像研究。小鼠静脉注射 18F-FIAU 或 18F-FAU。在注射后 65 分钟内对每只示踪剂进行动态成像，然后对一些动物进行额外的 150 分钟静态成像。在注射后 60 或 150 分钟处死动物。收集血液和组织样本进行生物分布和代谢物分析。在来自两个肿瘤的图像上画出感兴趣区域，以计算时间-活性曲线。
生物分布和成像研究表明，18F-FIAU 在 MH3924A-stb-tk+肿瘤中的摄取最高。动态成像研究显示，HSV-TK 表达肿瘤中 18F-FIAU 在 60 分钟内持续积累。MH3924A-stb-tk+肿瘤的平均生物分布值（SUV ± SE）分别为 2.07 ± 0.40 和 6.15 ± 1.58，MH3924A 肿瘤的分别为 0.19 ± 0.07 和 0.47 ± 0.06，分别在 60 分钟和 150 分钟。在注射 18F-FIAU 的小鼠中，在 60 分钟时，血液中近 63%的活性以其代谢产物 18F-FAU 的形式存在。用 18F-FAU 进行的成像和生物分布研究表明，在 MH3924A-stb-tk+肿瘤中没有任何特异性积聚，并且两种肿瘤的 SUV 与肌肉观察到的相似。
18F-FIAU 在 HSV-TK 表达肿瘤中表现出持续的活性积累。18F-FAU 不会在 HSV-TK 表达肿瘤中表现出任何优先积聚。在 18F-FIAU 治疗的小鼠中，18F-FAU 对 HSV-TK 阳性肿瘤中总摄取的贡献最小。
