11C-clomipramine: synthesis and analysis

A method is described for the labelling of the antidepressant clomipramine with 11C. One of the methyl groups of the side chain of clomipramine is labelled by metylation of mono-desmethyl clomipramine with 11C-formaldehyde in dimethylformamide (DMF) in the presence of formic acid according to Leuckarts' reaction, modified by CLARKE. The effects of reaction time, temperature and the concentrations of formic acid, water, formaldehyde and monodesmethyl-clomipramine was studied that optimum yield is obtained with a temperature of about 100 deg C for 10 min. Impurities appear at higher temperatures and the reaction is too slow at lower temperatures. Following labelling with 11C, 10 to 20 mCi of injectable 11C-clomipramine was obtained. The time required for synthesis, purification and streilization is 40 minutes. An injection into a human subject for a subsequent brain scan usually involves 10 to 15 mCi of substance, corresponding to 60 to 100 μg of clomipramine. The 11C-labelled product is chemically and radiochemically pure. (T.G.)