Regional brain kinetics of 6-fluoro-(beta-11C)-L-dopa and (beta-11C)-L-dopa following COMT inhibition. A study in vivo using positron emission tomography.

The regional brain kinetics of (beta-11C)-L-dopa and 6-fluoro-(beta-11C)-L-dopa was measured in six Rhesus monkeys using positron emission tomography (PET). Radioactivity accumulated specifically in the striatal region and the increase in L-dopa-derived radioactivity utilization with time was calculated using surrounding brain as a reference area, this being devoid of dopaminergic activity. The rate constant for selective striatal utilization i.e. grossly decarboxylation was 0.0110 +/- 0.0007 (S.D) and 0.0057 +/- 0.0006 min-1 for (beta-11C)-L-dopa and 6-fluoro-(beta-11C)-L-dopa, respectively. After pretreatment of the monkeys with the peripherally and centrally active catecholamine-O-methyl transferase (COMT) inhibitor Ro 40-7592 10 mg/kg, the decarboxylation rate remained unchanged (0.0112 +/- 0.0015 min-1) for (beta-11C)-L-dopa, whereas an increase in rate was measured for 6-fluoro-(beta-11C)-L-dopa (0.0092 +/- 0.0015 min-1). Differences in the distribution of radiolabelled metabolites i.e. the corresponding O-methyl-L-dopa in the reference area is most probably the reason for the difference in calculated decarboxylation rate seen between the radiotracers. The higher decarboxylation rate measured for 6-fluoro-(beta-11C)-L-dopa after blockade of COMT shows that the radiolabelled metabolites i.e. 6-fluoro-O-methyl-(beta-11C)-L-dopa significantly contributes to background radioactivity.