Okamura Toshimitsu, Okada Maki, Kikuchi Tatsuya, Wakizaka Hidekatsu, Zhang Ming-Rong
Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
J Cereb Blood Flow Metab. 2015 Dec;35(12):1930-6. doi: 10.1038/jcbfm.2015.132. Epub 2015 Jun 17.
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 (11)C-labeled dihydroquinoline derivative ([(11)C]DHQ1) for positron emission tomography (PET). The lipophilic PET tracer [(11)C]DHQ1 was rapidly oxidized to its hydrophilic form in mouse brain homogenate. The redox modulators diphenyleneiodonium and apocynin significantly reduced the initial velocity of [(11)C]DHQ1 oxidation, and apocynin also caused concentration-dependent inhibition of the initial velocity. Moreover, [(11)C]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 [(11)C]DHQ1 to the hydrophilic cationic form, leading to a rapid decrease of radioactivity in the brain. Thus, the difference in the [(11)C]DHQ1 kinetics reflects the alteration in redox status caused by apocynin. In conclusion, [(11)C]DHQ1 is a potential PET tracer for imaging of redox status in the living brain.
氧化还原平衡紊乱与多种疾病的发病机制有关。本研究旨在探讨使用（11）C标记的二氢喹啉衍生物（[(11)C]DHQ1）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[(11)C]DHQ1在小鼠脑匀浆中迅速氧化为其亲水性形式。氧化还原调节剂二苯基碘鎓和载脂蛋白显著降低了[(11)C]DHQ1氧化的初始速度，载脂蛋白还引起了初始速度的浓度依赖性抑制。此外，[(11)C]DHQ1给药后通过扩散容易进入大脑，并氧化为亲水性阳离子形式，然后缓慢下降。相比之下，载脂蛋白治疗抑制了[(11)C]DHQ1在体内氧化为亲水性阳离子形式，导致大脑中放射性迅速下降。因此，[(11)C]DHQ1动力学的差异反映了载脂蛋白引起的氧化还原状态的改变。总之，[(11)C]DHQ1是一种用于活体脑氧化还原状态成像的潜在PET示踪剂。
