FLUORODOPA POSITRON EMISSION TOMOGRAPHY WITH AN INHIBITOR OF CATECHOL-O-METHYLTRANSFERASE - EFFECT OF THE PLASMA 3-O-METHYLDOPA FRACTION ONDATA-ANALYSIS

Fluorodopa (FDOPA) is an analogue of L-dihydroxyphenylalanine (L-dopa) used to assess the nigrostriatal dopamine system in vivo with positro n emission tomography (PET). However, FDOPA/PET quantitation is compli cated by the presence of the 3-O-methyl-FDOPA (30MFD fraction in brain and plasma, Pretreatment with entacapone (OR-611), a peripheral catec hol O-methyl-transferase (COMT) inhibitor, greatly reduces the plasma 30MFD fraction and provides an ideal situation to evaluate the contrib ution of the plasma 30MFD fraction in several kinetic models of FDOPA uptake. We performed FDOPA/PET with and without the OR-611 preadminist ration in six Parkinson's disease (PD) patients. We measured the time- course of the plasma FDOPA and 30MFD fractions using high-pressure liq uid chromatography (HPLC), We calculated striato-occipital ratios (SOR ), and estimated the striatal FDOPA uptake rate constant graphically u sing the plasma FDOPA and occipital tissue time activity curves (K-i(F D) and K-i(OCC), respectively). We also estimated striatal dopa decarb oxylase (DDC) activity (k(3)D) using a model incorporating independent measurements of 30MFD transport kinetic rate constants. With the prea dministration of OR-611, the pharmacological efficiency in plasma was prolonged significantly (21.1-37.7%; p < 0.01). We also observed signi ficant mean elevations in SOR and K-i(OOC) by 21.8 and 53.5%, respecti vely (p < 0.05). K-i(FD) and k(3)(D) 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.