Synthesis of 11C‐labeled ubiquinone and ubiquinol via Pd0‐mediated rapid C‐[11C]methylation using [11C]methyl iodide and 39‐demethyl‐39‐(pinacolboryl)ubiquinone. (8th January 2019)

• Record Type: Journal Article
• Authors: Goto, Miki; Nishiyama, Akira; Yamaguchi, Takao; Watanabe, Kyosuke; Fujii, Kenji; Watanabe, Yasuyoshi; Doi, Hisashi
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 62:Number 2(2019)
• Page Start: 86
• Page End: 94
• Publication Date: 2019-01-08
• Subjects: Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3700
• Languages: English
• ISSNs: 0362-4803

Abstract

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 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 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 Q10 . Abstract : With the objective of investigating the in vivo biological functions of coenzyme Q10, 11 C‐labeled ubiquinone and ubiquinol were synthesized by Pd‐mediated rapid C ‐[ 11 C]methylation using [ 11 C]methyl iodide. The organoborane precursor, 39‐demethyl‐39‐(pinacolboryl)ubiquinone, which is required for C ‐[ 11 C]methylation, was prepared by Ru‐catalyzed olefin metathesis using ubiquinone. This concept behind this procedure is that unradiolabeled natural ubiquinone undergoes chemical conversion to afford 11 C‐radiolabeled ubiquinone and ubiquinol.