Evaluation of Bias of the Influx Constant Estimated by Patlak Analysis for [¹⁸F] FDOPA PET: Influence of Metabolites for [¹⁸F] FDOPA

Abstract

Patlak analysis, which estimates the net FDOPA influx constant (K_i) 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_i 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_i estimated by Patlak analysis. For this purpose, we developed a model describing the detailed pathway of dopamine kinetics in the striatum, and a standard time-activity 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 K_i values estimated by Patlak analysis for these simulated TACs. K_i was increased when the dopamine metabolism to DOPAC (k₉^dopac) and the clearance of DOPAC and HVA (k₁₁^dopac, k₁₁^hva) were altered. The results suggest that K_i 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_i value estimated Patlak analysis.