We have studied the synthesis of [ 1 1 C]2,3-dimethoxy-5-methyl-6-(10-hydroxy)-decyl-1,4-benzoquinone (idebenone) and [ 1 1 C]2,3-dimethoxy-5-methyl-1,4-benzoquinone (CoQ 0 ) by methylation of their respective desmethyl precursors using [ 1 1 C]CH 3 I for in vivo measurement of mitochondrial electron transfer and redox state. The [ 1 1 C]idebenone was more lipophilic than [ 1 1 C]CoQ 0 ; the latter became hydrophilic by reduction. Clearance of [ 1 1 C]idebenone from mouse brain was more rapid than that of [ 1 1 C]CoQ 0 . The results indicated that modification of the isoprenoid side chain in [ 1 1 C]CoQ is necessary to develop more suitable radiopharmaceuticals.