Parkinson’s disease laterality: a 11C-PE2I PET imaging study

Abstract

Asymmetry of striatal dopaminergic deficits and motor symptoms is a typical characteristic of idiopathic Parkinson's disease (PD). This study aims to characterise the trend of asymmetry in moderate-stage PD. We performed a 19-month longitudinal study in 27 patients with PET-CT imaging and appropriate clinical assessments. 11 C-PE2I non-displaceable binding potential (BP ND) was calculated bilaterally for the striatum at baseline and follow-up to estimate the in vivo density of striatal dopamine transporters (DAT). Changes in striatal 11 C-PE2I BP ND over time were more prominent in the ipsilateral as compared to contralateral side. Changes in MDS-UPDRS-III (motor component of the Movement Disorders Society Unified PD Rating Scale) were not different between the clinically most and least affected body sides. Our data support that the asymmetry in striatal dopaminergic degeneration becomes less prominent in moderate-stage PD. In contrast, during the above period, the asymmetry of motor symptoms was maintained between the clinically most and least affected body sides.

Longitudinal Positron Emission Tomography Imaging of Presynaptic Terminals in Early Parkinson's Disease

“…This lack of correlation between longitudinal changes in 18 F‐FE‐PE2I binding and motor scores is consistent with previous longitudinal studies with 18 F‐dopa PET and 123 I‐β‐CIT or 123 I‐FP‐CIT‐SPECT 3‐8 . By contrast, two recent studies by Piccini and colleagues did find significant correlations between 19‐month longitudinal changes in striatal 18 F‐FE‐PE2I binding and motor scores 9,19 . A possible explanation for this discrepancy is that the patients in the studies by Piccini and colleagues had more advanced PD, with longer average BL disease duration since diagnosis (>5 years compared with approximately 2 years in our study) and substantially higher BL average motor scores off medication (MDS‐UPDRS‐III score of approximately 40 after conversion from UPDRS‐III score, 26 compared with 24 in our study) 9,19 .…”

“…9,19 A possible explanation for this discrepancy is that the patients in the studies by Piccini and colleagues had more advanced PD, with longer average BL disease duration since diagnosis (>5 years compared with approximately 2 years in our study) and substantially higher BL average motor scores off medication (MDS-UPDRS-III score of approximately 40 after conversion from UPDRS-III score, 26 compared with 24 in our study). 9,19 There is evidence that DAT downregulation occurs mostly in early PD and that this compensatory mechanism breaks down as the disease progresses. 38,45 Compensatory DAT downregulation may thus have been a stronger confounder in our study than in the more advanced patients studied by Piccini et al…”

“…17,18 Two longitudinal 11 C-PE2I PET studies in PD reported significant correlations between change in 11 C-PE2I BP ND and change in Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) or Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) scores over 19 months, suggesting that PE2I PET could provide a surrogate biomarker for motor progression. 9,19 Longitudinal PE2I PET data in healthy controls have not been reported. 11 C-UCB-J is another novel PET radioligand that could potentially be useful for monitoring PD progression.…”

Molecular Imaging in Parkinsonian Disorders—What’s New and Hot?

“…Greater loss of striatal DAT in the (least-affected) hemisphere ipsilateral to the clinically most affected body side was also demonstrated in a longitudinal PET study using 11C-PE2I, while striatal asymmetry gradually became less prominent despite the persistence of clinical asymmetry [ 14 ]. In addition, integration of DAT decline rate in the putamen using SPECT enables to impute the start of dopaminergic degeneration to around 10 years before motor onset in the Parkinson’s Progression Markers Initiative (PPMI) cohort [ 15 ].…”

“…In particular, lower striatal D2R binding was found in a meta-analysis for PSP and MSA-P patients in comparison to PD patients (14.2% and 21.8%, respectively), contrasting with an initial upregulation of striatal D2-receptors in PD patients up to 4 years after the onset of motor symptoms [ 54 ]. Overall, multiple studies indicate that dopaminergic degeneration is more symmetric in degenerative parkinsonian disorders other than PD, although this finding is not decisive for individual diagnosis and loses its importance as asymmetry is gradually reduced in moderate and advanced PD [ 14 , 55 ]. As such, greater regional dopaminergic asymmetry likely involved the nigrostriatal pathway in PD patients, whereas asymmetry was restricted to the bilateral caudate in patients with DLB and to the pallido-subthalamic pathway in patients with PSP [ 56 ].…”