PET imaging of 11C-labeled coenzyme Q10: Comparison of biodistribution between [11C]ubiquinol-10 and [11C]ubiquinone-10.
PET imaging of 11C-labeled coenzyme Q10: Comparison of biodistribution between [11C]ubiquinol-10 and [11C]ubiquinone-10.
复制标题
11C 标记的辅酶 Q10 的 PET 成像：[11C]ubiquinol-10 和 [11C]ubiquinone-10 之间的生物分布比较。
DOI：
10.1016/j.bbrc.2019.03.073
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Watanabe Y.
中科院分区：
文献类型：
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作者：
Watanabe K;Nozaki S;Goto M;Kaneko KI;Hayashinaka E;Irie S;Nishiyama A;Kasai K;Fujii K;Wada Y;Mizuno K;Mizuseki K;Doi H;Watanabe Y.
辅酶Q10（CoQ 10）不仅作为线粒体电子传递链中的重要电子载体，而且作为抗氧化剂保护细胞免受氧化应激。辅酶Q10补充剂预计对多种疾病有效。辅酶Q10的主要形式是泛醇-10（还原形式）和泛醌-10（氧化形式）。两种形式的辅酶Q10补充剂都是市售的，然而，它们的动力学差异仍然不清楚。为了对泛醇-10和泛醌-10的动力学进行体内分析，我们成功地合成了11 C标记的泛醇-10（[11 C]UQL）和泛醌-10（[11 C]UQN）。在本研究中，我们旨在研究[11 C]UQL和[11 C]UQN的动力学，这两种药物均通过8周龄雄性Sprague-Dawley大鼠的尾静脉给药。进行全身正电子发射断层扫描（PET）成像，以跟踪肝、脾、脑和其他器官中蓄积的时间过程。然后，在注射后20或90 min的两个典型时间点，我们进行了生物分布研究。采集各种器官/组织和血液，称重并使用伽马计数器计数。计算每克组织的注射剂量百分比（%ID/g），作为每种化合物蓄积的指标。结果，在两个时间点，大脑、小脑、白色脂肪组织、肌肉、肾脏和睾丸中[11 C]UQL的%ID/g较高（P< 0.05）：在90 min时间点，棕色脂肪组织中[11 C]UQL的%ID/g较高与[11 C]UQN相比，[11 C] UQN在90 min时的脾脏中的%ID/g显著降低（P< 0.05）。在血浆中代谢物分析的单独研究中，注射到大鼠尾静脉中的UQL在PET扫描期间几乎没有变化，但UQN逐渐转化为还原型UQL。因此，UQL进入组织和器官的摄取值是相当准确的，但UQN的摄取值可能是UQN摄取和部分转换的UQL摄取的总和。这些研究表明，辅酶Q10的积累水平取决于其氧化还原状态，辅酶Q10的氧化还原状态可能是优化有效补充的关键。
Coenzyme Q10(CoQ10) plays a key role not only as an essential electron carrier in the mitochondrial electron transport chain, but also as an antioxidant to protect cells from oxidative stress. CoQ10supplementation is expected to be effective for a variety of diseases. The predominant forms of CoQ10are the ubiquinol-10 (reduced form) and ubiquinone-10 (oxidized form). Both forms of CoQ10supplements are commercially available, however, their kinetic difference is still unclear. In order to conductin vivoanalysis of the kinetics of ubiquinol-10 and ubiquinone-10, we succeeded in synthesizing11C-labeled ubiquinol-10 ([11C]UQL) and ubiquinone-10 ([11C]UQN), respectively. In the present study, we aimed to investigate the kinetics of [11C]UQL and [11C]UQN, both of which were administered via the tail vein of 8-week-old male Sprague-Dawley rats. Whole-body positron emission tomography (PET) imaging was performed to follow the time course of accumulation in the liver, spleen, brain, and other organs. Then, at the two typical time points at 20 or 90 min after injection, we conducted the biodistribution study. Various organs/tissues and blood were collected, weighed and counted with a gamma counter. Percent injected dose per gram of tissue (%ID/g) was calculated as the indicator of the accumulation of each compound. As the results, at both time points, %ID/g of [11C]UQL in the cerebrum, cerebellum, white adipose tissue, muscle, kidney, and testis were higher (P< 0.05) than that of [11C]UQN: at 90-min time point, %ID/g of [11C]UQL in the brown adipose tissue was higher (P< 0.05) than that of [11C]UQN: on the contrary, %ID/g of [11C]UQL in the spleen was lower (P< 0.05) than that of [11C]UQN at 90 min. In a separate study of the metabolite analysis in the plasma, UQL injected into the tail vein of rats was almost unchanged during the PET scanning time, but UQN was gradually converted to the reduced form UQL. Therefore, the uptake values of UQL into the tissues and organs were rather accurate but those of UQN might be the sum of UQN uptake and partly converted UQL uptake. These studies suggested that the accumulation level of administered CoQ10differs depending on its redox state, and that CoQ10redox state could be crucial for optimization of the effective supplementation.