A 11C-labeled 1,4-dihydroquinoline derivative as a potential PET tracer for imaging of redox status in mouse brain
A 11C-labeled 1,4-dihydroquinoline derivative as a potential PET tracer for imaging of redox status in mouse brain
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DOI：
10.1038/jcbfm.2015.132
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发表时间：
2015-12-01
影响因子：
6.3
通讯作者：
Zhang, Ming-Rong
中科院分区：
文献类型：
--
作者：
Okamura, Toshimitsu;Okada, Maki;Zhang, Ming-Rong
氧化还原平衡的紊乱与许多疾病的发病机制有关。本研究旨在探讨使用C-11标记的二氢喹啉衍生物（[C-11] DHQ 1）进行正电子发射断层扫描（PET）成像脑氧化还原状态的可行性。亲脂性PET示踪剂[C-11] DHQ 1在小鼠脑匀浆中迅速氧化成其亲水形式。氧化还原调节剂diphenyleneiodonium和夹竹桃素显着降低[11 C] DHQ 1氧化的初始速度，夹竹桃素也引起浓度依赖性抑制的初始速度。此外，[C-11] DHQ 1在给药后容易通过扩散进入脑，并氧化成亲水性阳离子形式，然后缓慢降低。相比之下，夹竹桃麻素处理抑制[C-11] DHQ 1在体内氧化成亲水性阳离子形式，导致脑中放射性的快速降低。因此，[C-11] DHQ 1动力学的差异反映了由夹竹桃麻素引起的氧化还原状态的改变。总之，[C-11] DHQ 1是一种潜在的PET示踪剂，可用于活体脑中氧化还原状态的成像。
A disturbance in redox balance has been implicated in the pathogenesis of a number of diseases. This study sought to examine the feasibility of imaging brain redox status using a C-11-labeled dihydroquinoline derivative ([C-11]DHQ1) for positron emission tomography (PET). The lipophilic PET tracer [C-11]DHQ1 was rapidly oxidized to its hydrophilic form in mouse brain homogenate. The redox modulators diphenyleneiodonium and apocynin significantly reduced the initial velocity of [11C]DHQ1 oxidation, and apocynin also caused concentration-dependent inhibition of the initial velocity. Moreover, [C-11]DHQ1 readily entered the brain by diffusion after administration and underwent oxidation into the hydrophilic cationic form, which then slowly decreased. By contrast, apocynin treatment inhibited the in vivo oxidation of [C-11]DHQ1 to the hydrophilic cationic form, leading to a rapid decrease of radioactivity in the brain. Thus, the difference in the [C-11]DHQ1 kinetics reflects the alteration in redox status caused by apocynin. In conclusion, [C-11]DHQ1 is a potential PET tracer for imaging of redox status in the living brain.