Synthesis of ¹¹C‐labeled ubiquinone and ubiquinol via Pd⁰‐mediated rapid C‐[¹¹C]methylation using [¹¹C]methyl iodide and 39‐demethyl‐39‐(pinacolboryl)ubiquinone

Abstract

To enable positron emission tomography (PET) imaging of the in vivo kinetics of ubiquinone and ubiquinol, which is referred to as coenzyme Q10, their 11C‐radiolabeled counterparts were synthesized herein. 11C‐Labeled ubiquinone [11C]‐1 was realized by Pd‐mediated rapid C‐[11C]methylation of [11C]CH3I with 39‐demethyl‐39‐(pinacolboryl)ubiquinone, prepared by Ru‐catalyzed olefin metathesis of unradiolabeled ubiquinone with 2‐(pinacolboryl)propene. Subsequent reduction of [11C]‐1 using Na2S2O4 yielded 11C‐labeled ubiquinol [11C]‐2. The synthesis time and [11C]CH3I‐based radiochemical yield of [11C]‐1 were within 36 minutes and up to 53%, while those of [11C]‐2 were within 38 minutes and up to 39%, respectively. After radiopharmaceutical formulation, the qualities of [11C]‐1 and [11C]‐2 were confirmed to be applicable for animal PET studies. The analytical values of [11C]‐1 and [11C]‐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 11C‐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.

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

“…Particularly, [ 11 C]­ubiquinol was obtained in 38 min of radiosynthesis with 39% RCY and 95% RCP but 77% chemical purity, achieving 0.16–1.4 GBq of product with A m of 48–76 GBq/μmol. Noteworthy, in this case, the final reformulation included ascorbic acid to partially avoid [ 11 C]­ubiquinol degradation …”