Influence of O-Methylated Metabolite Penetrating the Blood–Brain Barrier to Estimation of Dopamine Synthesis Capacity in Human L-[β-11C]DOPA PET

O-methyl metabolite (L-[ β- 11 C]OMD) of 11 C-labeled L-3,4-dihydroxyphenylalanine (L-[ β- 11 C]DOPA) can penetrate into brain tissue through the blood–brain barrier, and can complicate the estimation of dopamine synthesis capacity by positron emission tomography (PET) study with L-[ β- 11 C]DOPA. We evaluated the impact of L-[ β- 11 C]OMD on the estimation of the dopamine synthesis capacity in a human L-[ β- 11 C]DOPA PET study. The metabolite correction with mathematical modeling of L-[ β- 11 C]OMD kinetics in a reference region without decarboxylation and further metabolism, proposed by a previous [ 18 F]FDOPA PET study, were implemented to estimate radioactivity of tissue L-[ β- 11 C]OMD in 10 normal volunteers. The component of L-[ β- 11 C]OMD in tissue time-activity curves (TACs) in 10 regions were subtracted by the estimated radioactivity of L-[ β- 11 C]OMD. To evaluate the influence of omitting blood sampling and metabolite correction, relative dopamine synthesis rate ( k ref ) was estimated by Gjedde–Patlak analysis with reference tissue input function, as well as the net dopamine synthesis rate ( K i ) by Gjedde–Patlak analysis with the arterial input function and TAC without and with metabolite correction. Overestimation of K i was observed without metabolite correction. However, the k ref and K i with metabolite correction were significantly correlated. These data suggest that the influence of L-[ β- 11 C]OMD is minimal for the estimation of k ref as dopamine synthesis capacity.