6-([F]氟乙酰氨基)-1-己酰基苯胺正电子发射断层显像术在化疗诱导的神经毒性中检测组蛋白去乙酰化酶活性改变的研究。
6-([F]Fluoroacetamido)-1-hexanoicanilide PET Imaging of Altered Histone Deacetylase Activity in Chemotherapy-Induced Neurotoxicity.
机构信息
Proton Medical Research Center, University of Tsukuba, Tsukuba, Japan.
Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
出版信息
Contrast Media Mol Imaging. 2018 Mar 20;2018:3612027. doi: 10.1155/2018/3612027. eCollection 2018.
BACKGROUND
Histone deacetylases (HDACs) regulate gene expression by changing histone deacetylation status. Neurotoxicity is one of the major side effects of cisplatin, which reacts with deoxyribonucleic acid (DNA) and has excellent antitumor effects. Suberoylanilide hydroxamic acid (SAHA) is an HDAC inhibitor with neuroprotective effects against cisplatin-induced neurotoxicity.
PURPOSE
We investigated how cisplatin with and without SAHA pretreatment affects HDAC expression/activity in the brain by using 6-([F]fluoroacetamido)-1-hexanoicanilide ([F]FAHA) as a positron emission tomography (PET) imaging agent for HDAC IIa.
MATERIALS AND METHODS
[F]FAHA and [F]fluoro-2-deoxy-2-D-glucose ([F]FDG) PET studies were done in 24 mice on 2 consecutive days and again 1 week later. The mice were divided into three groups according to drug administration between the first and second imaging sessions (Group A: cisplatin 2 mg/kg, twice; Group B: cisplatin 4 mg/kg, twice; Group C: cisplatin 4 mg/kg, twice, and SAHA 300 mg/kg pretreatment, 4 times).
RESULTS
The value of [F]FAHA was increased and the percentage of injected dose/tissue g (% ID/g) of [F]FDG was decreased in the brains of animals in Groups A and B. The value of [F]FAHA and % ID/g of [F]FDG were not significantly different in Group C.
CONCLUSIONS
[F]FAHA PET clearly showed increased HDAC activity suggestive of cisplatin neurotoxicity , which was blocked by SAHA pretreatment.
背景
组蛋白去乙酰化酶（HDACs）通过改变组蛋白去乙酰化状态来调节基因表达。顺铂的神经毒性是其主要的副作用之一，它与脱氧核糖核酸（DNA）反应，具有优异的抗肿瘤作用。丁酸钠（SAHA）是一种 HDAC 抑制剂，对顺铂诱导的神经毒性具有神经保护作用。
目的
我们使用 6-([F]氟乙酰氨基）-1-己烷甲酰胺([F]FAHA)作为 HDAC IIa 的正电子发射断层扫描（PET）成像剂，研究顺铂联合和不联合 SAHA 预处理对大脑中 HDAC 表达/活性的影响。
材料和方法
在连续 2 天和 1 周后，对 24 只小鼠进行[F]FAHA 和[F]氟-2-脱氧-2-D-葡萄糖([F]FDG) PET 研究。根据两次成像之间的药物治疗，将小鼠分为三组（A 组：顺铂 2mg/kg，2 次；B 组：顺铂 4mg/kg，2 次；C 组：顺铂 4mg/kg，2 次，SAHA 预处理 300mg/kg，4 次）。
结果
A 组和 B 组动物的[F]FAHA 值增加，[F]FDG 的组织 g 注射剂量百分比（% ID/g）降低。C 组的[F]FAHA 值和[F]FDG 的% ID/g 无显著差异。
结论
[F]FAHA PET 清楚地显示了 HDAC 活性的增加，提示顺铂的神经毒性，而 SAHA 预处理可以阻断这种毒性。
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