The pharmacokinetic model of 18F-FDOPA in PET brain imaging for early Parkinson’s disease

Abstract

Parkinson’s disease (PD) symptom usually appears when over half of all dopaminergic neurons have died. Early detection and treatment approach are; therefore, very important. The 18F-FDOPA PET scan is extensively examined to differentiate the normal and pathological dopamine metabolism in the human brain. The purpose of this study was to investigate the transfer rate constants of 18F-FDOPA in PET brain imaging based on compartmental model in early Parkinson’s disease. The retrospective data from five early PD patients who underwent 18F-FDOPA PET brain scan at King Chulalongkorn Memorial Hospital (KCMH) were collected. After 18F-FDOPA was administered intravenously, PET images were acquired for 90 min using 3D list-mode and reconstructed into 5-min interval for obtaining each time-point image dataset. PET image data were co-registered and normalized with PET brain template on Statistical Parametric Mapping (SPM) software for segmenting the striatum, caudate and putamen. The activity concentration was subsequently measured at each side of the regions. Compartmental model and time-activity curve were generated using SAAM II simulation software to estimate transfer rate constants in each side. Regions at contralateral side to patient’s predominant symptoms were considered as PD and the ipsilateral side as control. A pharmacokinetic model consisting of 3 compartments and 3 transfer rate constants could adequately describe the kinetics 18F-FDOPA and its metabolites. By model fitting to the tissue kinetics, the mean FDOPA forward and reverse transport constant across the blood-brain barrier (K1 & k2), and the mean FDOPA decarboxylation rate constant (k3) in the contralateral striatum were K1 = 0.0231 ± 0.0081 ml min-1 g-1, k2 = 0.0196 ± 0.0054 min-1, and k3 = 0.0112 ± 0.0043 min-1 while the ipsilateral striatum were K1 = 0.0245 ± 0.0078 ml min-1 g-1, k2 = 0.0178 ± 0.0061 min-1, and k3 = 0.0152 ± 0.0053 min-1 respectively. For the contralateral caudate, K1 = 0.0094 ± 0.0030 ml min-1 g-1; k2 = 0.0237 ± 0.007 min-1; and k3 = 0.0203 ± 0.0077 min-1 while the ipsilateral, K1 = 0.0091 ± 0.0022 ml min-1 g-1; k2 = 0.0228 ± 0.0031 min-1; and k3 = 0.0215 ± 0.0094 min-1. In the contralateral putamen, K1 = 0.0116 ± 0.0037 ml min-1 g-1; k2 = 0.0268 ± 0.0057 min-1; and k3 = 0.0112 ± 0.003 min-1, while the ipsilateral, K1 = 0.0131 ± 0.0044 ml min-1 g-1; k2 = 0.0254 ± 0.0072 min-1; and k3 = 0.0176 ± 0.0025 min-1. Furthermore, K1 and k3 rate constants at the contralateral side of striatum and putamen were significantly lower than the another (p-value < 0.05). In contrast, there was no statistically significant difference in any transfer rate constants of caudate. The biokinetic data obtained in this study will be used as an initial reference report in Thai PD patients. Both K1 and k3 seemed to be the predictor parameters to distinguish between PD and normal patients.