PET imaging of 11C-labeled coenzyme Q10: Comparison of biodistribution between [11C]ubiquinol-10 and [11C]ubiquinone-10.

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. CoQ10 supplementation is expected to be effective for a variety of diseases. The predominant forms of CoQ10 are the ubiquinol-10 (reduced form) and ubiquinone-10 (oxidized form). Both forms of CoQ10 supplements are commercially available, however, their kinetic difference is still unclear. In order to conduct in vivo analysis of the kinetics of ubiquinol-10 and ubiquinone-10, we succeeded in synthesizing 11C-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 CoQ10 differs depending on its redox state, and that CoQ10 redox state could be crucial for optimization of the effective supplementation.

Imaging mass spectrometry analysis of ubiquinol localization in the mouse brain following short-term administration.

We analyzed the localization of ubiquinol, the reduced form of coenzyme Q10 (Re-CoQ10), in mouse brain sections using matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance imaging mass spectrometry (IMS) to evaluate the effect of dietary Re-CoQ10 in mouse brain. Mice were orally administered Re-CoQ10 for 14 days and brain Re-CoQ10 content was subsequently quantified using liquid chromatography-mass spectrometry. IMS was employed to visualize Re-CoQ10 at a resolution of 150 µm in the mouse brain. Increased Re-CoQ10 was observed in the corpus callosum, hippocampus, midbrain, cerebellum, brain stem, substantia nigra and striatum. These regions are related to movement, memory and vital life functions. Thus, we demonstrated the effect of Re-CoQ10 administration on the specific localization of Re-CoQ10 in the brain.

Stability of ubiquinol-10 (reduced form of coenzyme Q10 ) in human blood.

The ratio of ubiquinol-10 in total coenzyme Q10 (TQ10 ) in human plasma has been proposed as a useful biomarker of oxidative stress. Since ubiquinol-10 is easily oxidized in air, it is necessary to perform suitable processing at medical institutions prior to analysis. To establish stable storage conditions for blood to determine the ubiquinol-10/TQ10 ratios properly, the effects of temperature conditions on the stability of ubiquinol-10 were studied. Blood samples were collected from nine male Japanese volunteers. Changes in ubiquinol-10/TQ10 ratios in blood samples were evaluated under three temperature conditions (room temperature, refrigerated and ice-cooled). Plasma levels of ubiquinol-10 and ubiquinone-10 were determined by an HPLC system with electrochemical detection and the ubiquinol-10/TQ10 ratios were calculated. We found that the ubiquinol-10/TQ10 ratio was stable up to 8 or 4 h when blood samples were stored in refrigerator or ice-cold container, respectively, and its decreases during these periods were <1.0%. We conclude that, in order to evaluate ubiquinol-10/TQ10 ratios, blood samples should be stored in a refrigerator or an ice-cold container, and processed for plasma separation within 4 h.