Evaluation of bias of the influx constant estimated by Patlak analysis for [¹⁸F]FDOPA PET: Influence of metabolites for [¹⁸F] FDOPA

Patlak analysis, which estimates the net FDOPA influx constant (Ki by linear regression of data acquired from [¹⁸F] FDOPA PET study, is widely employed in the diagnosis of neurological disorder, such as Parkinson's disease. In K estimation by Patlak analysis, it is assumed that the metabolites of radioligand do not diffuse out of the tissue during PET scan. However, [ ¹⁸F] F-Dopamine, synthesized from [¹⁸F] FDOPA, is rapidly metabolized and its metabolites diffuse from the tissue. We aimed at the evaluation of the effect of dopamine metabolism and the clearance of its metabolites on K estimated by Patlak analysis. For this purpose, we developed a model describing the detailed pathway of dopamine kinetics in the striatum, and a standard timeactivity curve (TAC) was generated based on this model and [ ¹⁸F] FDOPA PET data of a monkey. And TACs in case of altering the dopamine metabolism or the clearance of its metabolites were simulated.Then, we evaluated K₁, values estimated by Patlak analysis for these simulated TACs. K was increased when the dopamine metabolism to DOPAC (κ ^dopac₉) and the clearance of DOPAC and HVA (AfTc, k\?) were altered. The results suggest that K could be biased by the influence of the metabolism of dopamine and clearance of its metabolites. Therefore, it is important to consider these biases in the interpretation of K value estimated Patlak analysis.