18F-dopa PET measuring aromatic l-amino acid decarboxylase activity is regarded as the gold standard for evaluating dopaminergic function in Parkinson's disease. Radioligands for dopamine transporters are also used in clinical trials and for confirming PD diagnosis. Currently, it is not clear which imaging marker is more reliable for assessing clinical severity and rate of progression. The objective of this study was to directly compare 18F-dopa with the highly selective dopamine transporter radioligand 11C-PE2I for the assessment of motor severity and rate of progression in PD. Thirty-three mild-moderate PD patients underwent 18F-dopa and 11C-PE2I PET at baseline. Twenty-three were followed up for 18.8 ± 3.4 months. Standard multiple regression at baseline indicated that 11C-PE2I BPND predicted UPDRS-III and bradykinesia-rigidity scores (P < 0.05), whereas 18F-dopa Ki did not make significant unique explanatory contributions. Voxel-wise analysis showed negative correlations between 11C-PE2I BPND and motor severity across the whole striatum bilaterally. 18F-Dopa Ki clusters were restricted to the most affected putamen and caudate. Longitudinally, negative correlations were found between striatal (increment)11C-PE2I BPND, (increment)UPDRS-III, and (increment)bradykinesia-rigidity, whereas no significant associations were found for (increment)18F-dopa Ki. One cluster in the most affected putamen was identified in the longitudinal voxel-wise analysis showing a negative relationship between (increment)11C-PE2I BPND and (increment)bradykinesia-rigidity. Striatal 11C-PE2I appears to show greater sensitivity for detecting differences in motor severity than 18F-dopa. Furthermore, dopamine transporter decline is closely associated with motor progression over time, whereas no such relationship was found with aromatic l-amino acid decarboxylase. 11C-PE2I may be more effective for evaluating the efficacy of neuroprotective treatments in PD.
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