ROUTES OF ADMINISTRATION AND EFFECT OF CARBIDOPA PRETREATMENT ON 6-[F-18]FLUORO-L-DOPA PET SCANS IN NONHUMAN-PRIMATES/

In 6-[F-18]fluoro-L-dopa (Fdopa)/positron emission tomography (PET) st udies, carbidopa pretreatment increases the Fdopa bioavailability to t he brain and enhances the intensity of striatal PET images. Different PET research teams have used various carbidopa doses and routes of adm inistration in non-human primate studies. The purpose of this study wa s to examine the plasma profiles of carbidopa and the effect of the ro ute of administration of carbidopa on a Fdopa/PET scan. Cynomolgus mon keys were given carbidopa either orally (5 mg/kg), intraperitoneally ( 2.5 and 5 mg/kg) or intravenously (5 mg/kg) 60-90 min prior to the Fdo pa injection. Carbidopa-treated monkeys were compared to monkeys witho ut carbidopa treatment. No carbidopa was detected in the plasma sample s when it was given orally, possibly due to poor absorption in the gas trointestinal tract. In addition, the striatal and cortical activities were not statistically different from those of the untreated monkeys, indicating that little or no inhibition of the peripheral decarboxyla tion of Fdopa by carbidopa had taken place. When carbidopa was given i ntraperitoneally at a dose of 2.5 and 5 mg/kg and intravenously at 5 m g/kg, plasma carbidopa concentrations at the time of Fdopa injection w ere 0.95 +/- 0.26, 2.22 +/- 0.23 and 2.79 +/- 0.26 mu g/ml, respective ly. Because of inhibition of peripheral decarboxylation of Fdopa by ca rbidopa, more Fdopa was available for transport into the brain and as a result, both the striatal and cortical activities were significantly higher than those of the untreated monkeys, Carbidopa administration had no effect on either the striatal-to-cortical activity ratio or the striatum uptake value.