Synthesis, Radiosynthesis, and in vitro Studies on Novel Hypoxia PET Tracers Incorporating [ 18 F]FDR
Synthesis, Radiosynthesis, and in vitro Studies on Novel Hypoxia PET Tracers Incorporating [ 18 F]FDR
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结合 [ 18 F]FDR 的新型缺氧 PET 示踪剂的合成、放射合成和体外研究
DOI：
10.1002/ejoc.202001670
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发表时间：
2021
影响因子：
2.8
通讯作者：
Musolino M
中科院分区：
文献类型：
--
作者：
Musolino M
我们报道了五种放射性示踪剂的合成，在缺氧反应的2 -硝基咪唑部分和5 - [18F] -氟脱氧核糖（[18F]FDR,12）假基之间含有不同的氧胺间隔剂：三个具有3,5,7个碳原子的线性烷基链（15 a - c），一个环丙基环（15 d）和一个1,4 -二取代- 1,2,3 -三唑（15 e）。在缺氧细胞中进行的实验表明，与金标准的缺氧示踪剂[18F]氟唑霉素阿拉伯糖（[18F]FAZA）和[18F]氟咪唑硝唑（[18F]FMISO）相比，15显示出优越的摄取动力学和对缺氧细胞的相似选择性。亲脂性和结构刚性对示踪剂15对缺氧细胞的选择性有很大影响：铅示踪剂15显示logP=0.38，是最刚性的间隔剂。第六种放射性示踪剂（15f），用2 - H -咪唑取代15d的2 -硝基咪唑部分，证明环丙基在对缺氧的敏感性中不起重要作用。
We report the synthesis of five radiotracers incorporating different oxyamine spacers between the hypoxia‐reactive 2‐nitroimidazole moiety and the 5‐[18F]‐fluorodeoxyribose ([18F]FDR,12) prosthetic group: three linear alkyl chains with 3, 5, 7 carbon atoms (15 a–c), a cyclopropyl ring (15 d) and a 1,4‐disubstituted‐1,2,3‐triazole (15 e). Experiments in hypoxic cells showed that15 ddisplays superior uptake kinetics – and similar selectivity for hypoxic cells – relative to the gold standard hypoxia tracers [18F]fluoroazomycin arabinoside ([18F]FAZA) and [18F]fluoromisonidazole ([18F]FMISO). Lipophilicity and structural rigidity have strong influence on the selectivity of tracers15towards hypoxic cells: the lead tracer15 ddisplays a logP=0.38 and the most rigid spacer. A sixth radiotracer (15 f), with a 2‐H‐imidazole replacing the 2‐nitroimidazole moiety of15 d, was used to demonstrate that the cyclopropyl group does not play a meaningful role in the sensitivity towards hypoxia.