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

Watanabe, Kyosuke; Nozaki, Satoshi; Goto, Miki; Kaneko, Ken‐ichi; Hayashinaka, Emi; Irie, Shin; Nishiyama, Akira; Kasai, Kazuhiko; Fukui, Kenji; Wada, Yasuhiro; Mizuno, Kei; Mizuseki, Kenji; Doi, Hisashi; Watanabe, Yasuyoshi

doi:10.1016/j.bbrc.2019.03.073

Cited by 10 publications

(13 citation statements)

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“…Since it has been considered that fatigue could potentially accelerate the oxidation of the central nervous system including these regions of the brain [ 60 ], the present results may suggest that ubiquinol intake may have inhibited intracerebral oxidation. Interestingly, when intracerebral uptake of ubiquinol and ubiquinone were verified using PET, the uptake level of ubiquinol was considerably higher than that of ubiquinone [ 61 ]. Therefore, improvements in fatigue, relaxation, cognitive function, and autonomic nerve function seen in the present study might also be greater with ubiquinol than with ubiquinone.…”

Section: Discussionmentioning

confidence: 99%

Ubiquinol-10 Intake Is Effective in Relieving Mild Fatigue in Healthy Individuals

et al. 2020

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Our double-blind, placebo-controlled study evaluated effects of ubiquinol, the reduced form of coenzyme Q10, on mild fatigue in healthy individuals experiencing fatigue in daily life that had continued for more than 1 and less than 6 months. The participants received 100-mg/day (Ubq100; age 44.0 ± 9.8 years; 14 females and 6 males) or 150-mg/day ubiquinol (Ubq150; age 40.4 ± 11.8 years; 14 females and 8 males) or placebo (Plc; age 41.3 ± 13.4 years; 13 females and 7 males) daily for 12 weeks. Measurements of subjective and objective fatigue were conducted by using questionnaires-based fatigue scales/visual analogue scales and autonomic nerve function/biological oxidation index, respectively, prior to the first dosing and every 4 weeks thereafter. Serum ubiquinol level increased three- to four-fold after 4 weeks and remained significantly higher than that after Plc administration throughout the intake period. Although a higher blood level of ubiquinol was observed with Ubq150 than with Ubq100, the difference was not statistically significant. In both Ubq100 and Ubq150 groups, subjective levels of fatigue sensation and sleepiness after cognitive tasks, which consisted of the modified Advanced Trail Making Test, the modified Stroop Color-Word Test, and the Digit Symbol Substitution Test, improved significantly compared with those in the placebo group, suggesting an anti-fatigue effect. The Ubq150 group demonstrated significant improvement compared with the Plc group regarding subjective level of relaxation after task, sleepiness before and after task, motivation for task, and serum level of oxidative stress. Correlation analysis between blood level of ubiquinol and each evaluated effect suggested a positive relationship with relaxation after task, motivation for cognitive task, and parasympathetic activity. The results of the study suggest that ubiquinol intake relieves mild fatigue in healthy individuals.

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Section: Discussionmentioning

confidence: 99%

Ubiquinol-10 Intake Is Effective in Relieving Mild Fatigue in Healthy Individuals

et al. 2020

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“…Furthermore, increased heart uptake of [ 11 C]CoQ 10 -liposomes, corrected for blood spillover of radioactivity, was registered, demonstrating incorporation of exogenous [ 11 C]CoQ 10 in normal myocardium over a short period (45 min) . More recently, biodistributions of the oxidized and reduced form of [ 11 C]CoQ 10 (ubiquinone-10 and ubiquinol-10 labeled at 39 positions) were evaluated in Sprague-Dawley rats . As shown in Figure , radiotracers mainly accumulated in the liver, lung, and spleen combined with an enhanced and persistent uptake in the heart, aortas, and head region for [ 11 C]ubiquinol.…”

Section: Enzyme Cofactors and Vitaminsmentioning

confidence: 99%

Radiosynthesis, Preclinical, and Clinical Positron Emission Tomography Studies of Carbon-11 Labeled Endogenous and Natural Exogenous Compounds

et al. 2022

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The presence of positron emission tomography (PET) centers at most major hospitals worldwide, along with the improvement of PET scanner sensitivity and the introduction of total body PET systems, has increased the interest in the PET tracer development using the short-lived radionuclides carbon-11. In the last few decades, methodological improvements and fully automated modules have allowed the development of carbon-11 tracers for clinical use. Radiolabeling natural compounds with carbon-11 by substituting one of the backbone carbons with the radionuclide has provided important information on the biochemistry of the authentic compounds and increased the understanding of their in vivo behavior in healthy and diseased states. The number of endogenous and natural compounds essential for human life is staggering, ranging from simple alcohols to vitamins and peptides. This review collates all the carbon-11 radiolabeled endogenous and natural exogenous compounds synthesised to date, including essential information on their radiochemistry methodologies and preclinical and clinical studies in healthy subjects.

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“…In vivo, cells can also depend on CoQ 10 transport from synthesizing organs like the liver. Studies of [ 3 H]‐radiolabeled or [ 11 C]‐labeled CoQ 10 distribution in rat tissues 74,75 showed that CoQ 10 is accumulated in blood, liver, and spleen, being very low in muscle, kidney, and brain, explaining why the last organs are the most affected by a CoQ 10 deficiency. The liver would be different, being an organ with a high synthesis capacity 76 and the highest efficiency to assimilate exogenous CoQ 10.…”

Section: Secondary Coenzyme Q10 Deficiency As a Mitochondrial Diseasementioning

confidence: 99%

“…The liver would be different, being an organ with a high synthesis capacity 76 and the highest efficiency to assimilate exogenous CoQ 10. 74,75 The levels of CoQ 10 in one specific organ can depend on two parameters: the capacity to produce its own CoQ 10 and the ability to assimilate CoQ 10 from other endogenous sources. The way these two parameters contribute to CoQ 10 levels can differ, depending on the organ's extent of differentiation or specialization, adding difficulty in understanding the disease severity.…”

Section: Secondary Coenzyme Q10 Deficiency As a Mitochondrial Diseasementioning

confidence: 99%

Secondary CoQ₁₀ deficiency, bioenergetics unbalance in disease and aging

et al. 2021

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Coenzyme Q10 (CoQ10) deficiency is a rare disease characterized by a decreased accumulation of CoQ10 in cell membranes. Considering that CoQ10 synthesis and most of its functions are carried out in mitochondria, CoQ10 deficiency cases are usually considered a mitochondrial disease. A relevant feature of CoQ10 deficiency is that it is the only mitochondrial disease with a successful therapy available, the CoQ10 supplementation. Defects in components of the synthesis machinery caused by mutations in COQ genes generate the primary deficiency of CoQ10. Mutations in genes that are not directly related to the synthesis machinery cause secondary deficiency. Cases of CoQ10 deficiency without genetic origin are also considered a secondary deficiency. Both types of deficiency can lead to similar clinical manifestations, but the knowledge about primary deficiency is deeper than secondary. However, secondary deficiency cases may be underestimated since many of their clinical manifestations are shared with other pathologies. This review shows the current state of secondary CoQ10 deficiency, which could be even more relevant than primary deficiency for clinical activity. The analysis covers the fundamental features of CoQ10 deficiency, which are necessary to understand the biological and clinical differences between primary and secondary CoQ10 deficiencies. Further, a more in‐depth analysis of CoQ10 secondary deficiency was undertaken to consider its origins, introduce a new way of classification, and include aging as a form of secondary deficiency.

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

Cited by 10 publications

References 13 publications

Ubiquinol-10 Intake Is Effective in Relieving Mild Fatigue in Healthy Individuals

Ubiquinol-10 Intake Is Effective in Relieving Mild Fatigue in Healthy Individuals

Radiosynthesis, Preclinical, and Clinical Positron Emission Tomography Studies of Carbon-11 Labeled Endogenous and Natural Exogenous Compounds

Secondary CoQ₁₀ deficiency, bioenergetics unbalance in disease and aging

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

Cited by 10 publications

References 13 publications

Ubiquinol-10 Intake Is Effective in Relieving Mild Fatigue in Healthy Individuals

Ubiquinol-10 Intake Is Effective in Relieving Mild Fatigue in Healthy Individuals

Radiosynthesis, Preclinical, and Clinical Positron Emission Tomography Studies of Carbon-11 Labeled Endogenous and Natural Exogenous Compounds

Secondary CoQ10 deficiency, bioenergetics unbalance in disease and aging

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Secondary CoQ₁₀ deficiency, bioenergetics unbalance in disease and aging