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PET imaging of 11C-labeled coenzyme Q10: Comparison of biodistribution between [11C]ubiquinol-10 and [11C]ubiquinone-10.
Biochem Biophys Res Commun. 2019 05 07; 512(3):611-615.BB

Abstract

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.

Authors+Show Affiliations

RIKEN Center for Life Science Technologies, Japan; RIKEN Center for Biosystems Dynamics Research, Japan; RIKEN Compass to Healthy Life Research Complex Program, Kobe, Hyogo, Japan; Osaka City University Graduate School of Medicine, Osaka, Japan. Electronic address: kyosuke.watanabe@riken.jp.RIKEN Center for Life Science Technologies, Japan; RIKEN Center for Biosystems Dynamics Research, Japan.RIKEN Center for Life Science Technologies, Japan; RIKEN Center for Biosystems Dynamics Research, Japan.RIKEN Center for Life Science Technologies, Japan; RIKEN Center for Biosystems Dynamics Research, Japan.RIKEN Center for Life Science Technologies, Japan; RIKEN Center for Biosystems Dynamics Research, Japan.RIKEN Center for Life Science Technologies, Japan; RIKEN Center for Biosystems Dynamics Research, Japan.KANEKA Corporation, Osaka, Japan.Takasago Analysis Center, Kaneka Techno Research Corporation, Takasago, Hyogo, Japan.KANEKA Corporation, Osaka, Japan.RIKEN Center for Life Science Technologies, Japan; RIKEN Center for Biosystems Dynamics Research, Japan.RIKEN Center for Life Science Technologies, Japan; RIKEN Center for Biosystems Dynamics Research, Japan; RIKEN Compass to Healthy Life Research Complex Program, Kobe, Hyogo, Japan; Osaka City University Graduate School of Medicine, Osaka, Japan.Osaka City University Graduate School of Medicine, Osaka, Japan.RIKEN Center for Life Science Technologies, Japan; RIKEN Center for Biosystems Dynamics Research, Japan.RIKEN Center for Life Science Technologies, Japan; RIKEN Center for Biosystems Dynamics Research, Japan; RIKEN Compass to Healthy Life Research Complex Program, Kobe, Hyogo, Japan. Electronic address: yywata@riken.jp.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30914201

Citation

Watanabe, Kyosuke, et al. "PET Imaging of 11C-labeled Coenzyme Q10: Comparison of Biodistribution Between [11C]ubiquinol-10 and [11C]ubiquinone-10." Biochemical and Biophysical Research Communications, vol. 512, no. 3, 2019, pp. 611-615.
Watanabe K, Nozaki S, Goto M, et al. PET imaging of 11C-labeled coenzyme Q10: Comparison of biodistribution between [11C]ubiquinol-10 and [11C]ubiquinone-10. Biochem Biophys Res Commun. 2019;512(3):611-615.
Watanabe, K., Nozaki, S., Goto, M., Kaneko, K. I., Hayashinaka, E., Irie, S., Nishiyama, A., Kasai, K., Fujii, K., Wada, Y., Mizuno, K., Mizuseki, K., Doi, H., & Watanabe, Y. (2019). PET imaging of 11C-labeled coenzyme Q10: Comparison of biodistribution between [11C]ubiquinol-10 and [11C]ubiquinone-10. Biochemical and Biophysical Research Communications, 512(3), 611-615. https://doi.org/10.1016/j.bbrc.2019.03.073
Watanabe K, et al. PET Imaging of 11C-labeled Coenzyme Q10: Comparison of Biodistribution Between [11C]ubiquinol-10 and [11C]ubiquinone-10. Biochem Biophys Res Commun. 2019 05 7;512(3):611-615. PubMed PMID: 30914201.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PET imaging of 11C-labeled coenzyme Q10: Comparison of biodistribution between [11C]ubiquinol-10 and [11C]ubiquinone-10. AU - Watanabe,Kyosuke, AU - Nozaki,Satoshi, AU - Goto,Miki, AU - Kaneko,Ken-Ichi, AU - Hayashinaka,Emi, AU - Irie,Satsuki, AU - Nishiyama,Akira, AU - Kasai,Kazuaki, AU - Fujii,Kenji, AU - Wada,Yasuhiro, AU - Mizuno,Kei, AU - Mizuseki,Kenji, AU - Doi,Hisashi, AU - Watanabe,Yasuyoshi, Y1 - 2019/03/23/ PY - 2019/03/07/received PY - 2019/03/13/accepted PY - 2019/3/28/pubmed PY - 2019/3/28/medline PY - 2019/3/28/entrez KW - Biodistribution KW - Coenzyme Q(10) KW - Metabolism KW - PET KW - Ubiquinol KW - Ubiquinone SP - 611 EP - 615 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 512 IS - 3 N2 - 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. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/30914201/PET_imaging_of_11C_labeled_coenzyme_Q10:_Comparison_of_biodistribution_between_[11C]ubiquinol_10_and_[11C]ubiquinone_10_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(19)30456-5 DB - PRIME DP - Unbound Medicine ER -