5-[18F]Fluoroalkyl pyrimidine nucleosides: probes for positron emission tomography imaging of herpes simplex virus type 1 thymidine kinase gene expression.
5-[18F]Fluoroalkyl pyrimidine nucleosides: probes for positron emission tomography imaging of herpes simplex virus type 1 thymidine kinase gene expression.
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DOI：
10.1016/j.nucmedbio.2008.10.009
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发表时间：
2009-01
影响因子：
3.1
通讯作者：
Kung, Hank F.
中科院分区：
文献类型：
--
作者：
Chacko, Ann-Marie;Blankemeyer, Eric;Lieberman, Brian P.;Qu, Wenchao;Kung, Hank F.
初步评价了新型5-[18F]氟烷基-2‘-脱氧尿苷([18F]FPrDU，[18F]FBuDU，[18F]FPeDU；[18F]1a-c)和2’-fluoro-2’-deoxy-5-[18F]fluoroalkyl-1-β-D-arabinofuranosyl尿嘧啶([18F]FFPrAU，[18F]FBuAU，[18F]FPeAU；[18F]1d-f)作为单纯疱疹病毒1型胸苷激酶(HSV1-tk)基因表达的探针的体内初步评价。以5-O-甲磺酸为原料和[18F]F-为原料，通过两步一锅亲核氟化反应，成功地合成了[18F]1a-f。在体内研究中，通过植入稳定表达HSV1-tk的RG2细胞(RG2TK+)和野生型细胞(RG2)在裸鼠体内种植肿瘤移植瘤。2小时P.I.的生物分布研究RG2TK+肿瘤对[18F]1a-b和[18F]1d-e的摄取与对照肿瘤无显著差异。然而，在RG2TK+肿瘤中，[18F]1c和[18F]1f的摄取率分别是对照RG2肿瘤的1.6倍和1.7倍。[18F]1c和[18F]1f的血液活动曲线突出了血液中放射性的快速清除。带有[18F]1c和[18F]1f的荷瘤小鼠的动态小动物PET(A-PET)成像研究显示，RG2TK+肿瘤的初始摄取率(分别是对照肿瘤的3.5倍和1.4倍)高于对照肿瘤，随着时间的推移，这两种肿瘤的活性持续消失。生物学评价表明，[18F]1c和[18F]1f对HSV1-tk基因表达的成像潜力有限，因为血液中的活性被快速洗掉，从而显著降低了示踪剂在表达HSV1-tk的肿瘤中积聚的敏感性和特异性。
The preliminary in vivo evaluation of novel 5-[18F]fluoroalkyl-2’-deoxyuridines ([18F]FPrDU, [18F]FBuDU, [18F]FPeDU; [18F]1a–c, respectively) and 2’-fluoro-2’-deoxy-5-[18F]fluoroalkyl-1-β-D-arabinofuranosyl uracils ([18F]FFPrAU, [18F]FFBuAU, [18F]FFPeAU; [18F]1d–f, respectively) as probes for imaging herpes simplex virus type-1 thymidine kinase (HSV1-tk) gene expression are described. [18F]1a–f were successfully synthesized by a rapid and efficient two step one-pot nucleophilic fluorination reaction using 5-O-mesylate precursors and [18F]F-. For in vivo studies, tumor xenografts were grown in nude mice by implanting RG2 cells stably expressing HSV1-tk (RG2TK+) and wild-type cells (RG2). Biodistribution studies at 2 h p.i. revealed that the uptake of [18F]1a–b and [18F]1d–e in RG2TK+ tumors was not significantly different from control tumors. However, [18F]1c and [18F]1f had an average 1.6 and 1.7–fold higher uptake in RG2TK+ tumors than control RG2 tumors. Blood activity curves for [18F]1c and [18F]1f highlight rapid clearance of radioactivity in the blood. Dynamic small animal PET (A-PET) imaging studies of tumor-bearing mice with [18F]1c and [18F]1f showed higher initial uptake (3.5–fold and 1.4–fold, respectively) in RG2TK+ tumors than control tumors, with continued washout of activity from both tumors over time. Biological evaluations suggest that [18F]1c and [18F]1f may have limited potential for imaging HSV1-tk gene expression due fast washout of activity from the blood thus significantly decreasing sensitivity and specificity of tracer accumulation in HSV1-tk expressing tumors.
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