Pharmacokinetic Modeling of 18F-FDOPA PET in the Human Brain for Early Parkinson's Disease

ABSTRACT

Objectives: Early detection is essential for the treatment approaches of Parkinson's disease (PD). Clinical criteria alone may be insufficient to distinguish early PD from other conditions. This study aimed to investigate the transfer rate constants of 6-18F-fluoro-L-dopa (18F-FDOPA) in positron emission tomography (PET) brain images as a sensitive parameter to detect early PD. Methods: Retrospective 18F-FDOPA PET data of five patients with early PD were collected. PET data were acquired for 90 min after intravenous injection of 306-379 MBq 18F-FDOPA, and reconstructed into a series of 18 five-minute frames. Reoriented PET images were coregistered and normalized with the PET brain template on the statistical parametric mapping. The 18F-FDOPA activity concentrations were measured in the striatum, caudate, and putamen on both sides Contralateral (as PD) and ipsilateral (as control) to the main motor symptoms. The pharmacokinetic model was generated using the SAAM II simulation software. The transfer rate constants across the blood-brain barrier (forward, K1 and reverse, k2) and decarboxylation rate constants (k3) were estimated in these regions. Results: The activity uptakes in the contralateral striatum (0.0323%±0.0091%) and putamen (0.0169%±0.0054%) were significantly lower than the control (0.0353%±0.0086%, 0.0199%±0.0054%, respectively). The K1 and k3 were significantly lower in the contralateral striatum and putamen (p<0.05). There were no significant differences in any transfer rate constants in the caudate. Conclusion: The transfer rate constants (K1 and k3) of 18F-FDOPA on the contralateral striatum and putamen were significantly lower than the control. These biokinetic data could be potential indicators for quantitative detection of early PD diagnosis.