A comparison of C-11-labeled L-DOPA and L-fluorodopa as positron emission tomography tracers for the presynaptic dopaminergic system

C-11-labeled 3,4-Dihydroxy-phenyl-L-alanine (L-DOPA) and L-fluorodopa were used as tracers for the functional state of the presynaptic dopamine system in anesthetized monkeys with positron emission tomography. The radiotracer disposition in brain tissue and plasma were studied and effects induced by pharmacologic challenges were evaluated. 6R-L-erythro-5,6,7,8-tetrahydrobi opterin (BR-BH4) increased the striatal influx rate constant, e.g., striata l K-i for L-[beta-(11) C]DOPA, but it induced no effect on the K-i-value us ing L-[beta-C-11]-6-fluorodopa. Studies of radiolabeled tracer and metaboli tes in plasma showed substantial differences between the two tracers. At ba seline conditions, 60% unchanged L-[beta-C-11]DOPA was detected in plasma 5 0 minutes after tracer injection and the 3-O-methylated fraction accounted for 25% of total radioactivity. For L-[beta-(11) C]-6-fluorodopa, the relat ion was inverse; about 25% unchanged tracer and 60% 3-O-methyl metabolite w ere present in plasma after 50 minutes. A site-specific C-11-labeling in th e carboxylic position in the molecules revealed a significant specific rete ntion of radioactivity in striatum with L-[carboxy C-11]-6-fluorodopa but n ot with L-[carboxy-l C-11]DOPA. The 3-O-methyl metabolite of L-DOPA is know n to pass the blood-brain barrier and may interfere with the calculation of the K-i value using a brain reference region. Thus, extensive 3-O-methylat ion in circulation of the fluorinated analog could obscure the detectabilit y of potential functional change in striatal K-i of the tracer when using a reference tissue model for calculation.