Abstract:
Carbidopa (L-alpha-hydrazino-alpha-methyl-b-(3,4-dihydroxyphenyl)
propionic acid is a known inhibitor of aromatic amino acid
decarboxylase. In both humans and monkeys, we studied the effects of
carbidopa on plasma and brain kinetics of 6-[18F]fluoro-L-DOPA (FDOPA),
an analog of L-DOPA used for PET studies of the central dopaminergic
system. Pretreatment with carbidopa resulted in increases in the plasma
levels of FDOPA and 3-O-methyl-6-[18F]fluoro-L-DOPA (3-OMFD). Total
striatal and cerebellar activities measured with PET were also
increased. Furthermore, increases observed in the specific striatal
activity (striatum minus cerebellum total activity) were correlated with
increases in the plasma FDOPA curve. Carbidopa pretreatment did not
affect the influx rate constant (K) for FDOPA from plasma to striatum in
humans as determined by Patlak graphical analysis. Thus, an increase in
measured striatal tomographic activity was secondary to the increase in
plasma FDOPA levels rather than as a result of changes in the FDOPA
influx rate constant