Synthesis of 11 C-labeled ubiquinone and ubiquinol via Pd 0 -mediated rapid C-[ 11 C] methylation using [ 11 C] methyl iodide and 39-demethyl-39-(pinacolboryl)ubiquinone.

To enable positron emission tomography (PET) imaging of the in-vivo kinetics of ubiquinone and ubiquinol, which is referred to as coenzyme Q10 , their 11 C-radiolabeled counterparts were synthesized herein. 11 C-Labeled ubiquinone [11 C]-1 was realized by Pd-mediated rapid C-[11 C] methylation of [11 C]CH3 I with 39-demethyl-39-(pinacolboryl) ubiquinone, prepared by Ru-catalyzed olefin metathesis of unradiolabeled ubiquinone with 2-(pinacolboryl)propene. Subsequent reduction of [11 C]-1 using Na2 S2 O4 yielded 11 C-labeled ubiquinol [11 C]-2. The synthesis time and [11 C]CH3 I-based radiochemical yield of [11 C]-1 were within 36 min and up to 53%, while those of [11 C]-2 were within 38 min and up to 39%, respectively. After radiopharmaceutical formulation, the qualities of [11 C]-1 and [11 C]-2 were confirmed to be applicable for animal PET studies. The analytical values of [11 C]-1 and [11 C]-2 are as follows: radioactivity up to 3.5 and 1.4 GBq, molar activity of 21-78 and 48-76 GBq/μmol, radiochemical purity of >99% and >99%, and chemical purity of >95% and 77%, respectively. The concept behind this radiolabeling procedure is that unradiolabeled natural ubiquinone can be converted to 11 C-radiolabeled ubiquinone and ubiquinol via a pinacolborane-substituted ubiquinone derivative. Each PET probe was used for molecular imaging using rats to investigate the in vivo kinetics and biodistribution of the coenzyme Q10 .