Abstract
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 (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]CH(3) 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 Na(2) S(2) O(4) yielded (11) C-labeled ubiquinol [(11) C]-2. The synthesis time and [(11) C]CH(3) I-based radiochemical yield of [(11) C]-1 were within 36 minutes and up to 53%, while those of [(11) C]-2 were within 38 minutes 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 of up to 3.5 and 1.4 GBq, molar activity of 21 to 78 and 48 to 76 GBq/μmol, 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 (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 Q(10) .