Synthesis of 11C-labeled ubiquinone and ubiquinol via Pd0-mediated rapid C-[11C]methylation using [11C]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 Q(10), their C-11-radiolabeled counterparts were synthesized herein. C-11-Labeled ubiquinone [C-11]-1 was realized by Pd-mediated rapid C-[C-11]methylation of [C-11]CH3I with 39-demethyl-39-(pinacolboryl)ubiquinone, prepared by Ru-catalyzed olefin metathesis of unradiolabeled ubiquinone with 2-(pinacolboryl)propene. Subsequent reduction of [C-11]-1 using Na2S2O4 yielded C-11-labeled ubiquinol [C-11]-2. The synthesis time and [C-11]CH3I-based radiochemical yield of [C-11]-1 were within 36 minutes and up to 53%, while those of [C-11]-2 were within 38 minutes and up to 39%, respectively. After radiopharmaceutical formulation, the qualities of [C-11]-1 and [C-11]-2 were confirmed to be applicable for animal PET studies. The analytical values of [C-11]-1 and [C-11]-2 are as follows: radioactivity of up to 3.5 and 1.4 GBq, molar activity of 21 to 78 and 48 to 76 GBq/mu mol, radiochemical purity of greater than 99% and greater than 95%, and chemical purity of greater than 99% and 77%, respectively. The concept behind this radiolabeling procedure is that unradiolabeled natural ubiquinone can be converted to C-11-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 Q(10).