SYNTHESIS OF (2-[C-11]METHOXY)ROTENONE, A MARKER OF MITOCHONDRIAL COMPLEX-I ACTIVITY

Recent studies suggest that defects in the function of the complexes o f the electron transport chain might be involved in the pathology of n eurological diseases such as mitochondrial encephalopathies, Parkinson 's, Huntington's and Alzheimer's disease. Rotenone is a potent reversi ble competitive inhibitor of complex I (NADH-CoQ reductase). To study the possible involvement of complex I in such diseases, we synthesized (2-[C-11]methoxy)rotenone by [C-11]alkylation of 2-O-desmethyl roteno ne methyl enol ether followed by hydrolysis of the enol ether to the k etone using aqueous trifluoroacetic acid. (2-[C-11]Methoxy)rotenone wa s purified by high pressure liquid chromatography (silica gel) and was obtained in 7-10% yields decay corrected to end of bombardment in syn thesis times typically shorter than 48 min. Radiochemical purities wer e over 95% and specific activities averaged 1000 Ci/mmol at end of syn thesis.