Flurodopa (FDOPA) is an analogue of L-di-hydroxyphenylalanine (L-dopa) used to 
assess the nigrostriatal dopamine system in vivo with positron emission 
tomography (PET). However, FDOPA/PET quantitation is complicated by the presence 
of the 3-O-methyl-FDOPA (3OMFD) fraction in brain and plasma. Pretreatment with 
entacapone (OR-611), a peripheral catechol O-methyl-transferase (COMT) 
inhibitor, greatly reduces the plasma 3OMFD fraction and provides an ideal 
situation to evaluate the contribution of the plasma 3OMFD fraction in several 
kinetic models of FDOPA uptake. We performed FDOPA/PET with and without the 
OR-611 preadministration in six Parkinson's disease (PD) patients. We measured 
the time-course of the plasma FDOPA and 3OMFD fractions using high-pressure 
liquid chromatography (HPLC). We calculated striato-occipital ratios (SOR), and 
estimated the striatal FDOPA uptake rate constant graphically using the plasma 
FDOPA and occipital tissue time activity curves (KiFD and KiOCC, respectively). 
We also estimated striatal dopa decarboxylase (DDC) activity (k3D) using a model 
incorporating independent measurements of 3OMFD transport kinetic rate 
constants. With the preadministration of OR-611, the pharmacological efficiency 
in plasma was prolonged significantly (21.1-37.7%; p < 0.01). We also observed 
significant mean elevations in SOR and KiOCC by 21.8 and 53.5%, respectively (p 
< 0.05). KiFD and k3D did not show significant change. We conclude that OR-611 
prolongs the circulation time of FDOPA in the plasma but does not alter rate 
constants for striatal FDOPA uptake or decarboxylation.