Quantification and discriminative power of 18F-FE-PE2I PET in patients with Parkinson’s disease

Delva, Aline; Weehaeghe, Donatienne Van; Aalst, June van; Ceccarini, Jenny; Baete, Kristof; Nuyts, Johan; Vandenberghe, Wim; Laere, Koen Van

doi:10.1007/s00259-019-04587-y

Cited by 27 publications

(37 citation statements)

References 16 publications

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“…26 Similarly, BP ND images for 18 F-FE-PE2I were calculated with the occipital cortex as the reference region. 21 Information on partial volume correction (PVC) can be found in the online supporting information.…”

Section: Discussionmentioning

confidence: 99%

“…To assess DAT binding, subjects underwent a 50 to 70 minutes postinjection static 18 F-FE-PE2I PET-MR scan on the simultaneous General Electric Signa 3T PET-MR. We previously demonstrated that this time window is optimal for group comparisons. 21 A mean activity of 107 ± 17 MBq F-FE-PE2I was injected. 18 F-FE-PE2I PET-MR in the patients with PD was performed on medication because antiparkinsonian drugs are considered not to interfere significantly with DAT imaging.…”

Section: Image Acquisitionmentioning

confidence: 99%

“…Here we performed 11 C‐UCB‐J PET in patients with early PD to assess the magnitude and anatomical extent of presynaptic terminal loss across the brain. In addition, we performed PET with the selective dopamine transporter (DAT) radioligand [18F]‐(E)‐N‐(3‐iodoprop‐2‐enyl)‐2β‐carbofluoroethoxy‐3β‐(4′‐methyl‐phenyl) nortropane ( 18 F‐FE‐PE2I), which permits measurement of presynaptic as well as somatodendritic DAT levels in dopaminergic neurons and thus allows a direct comparison of presynaptic versus somatodendritic damage within the nigrostriatal tract 13,19‐21 …”

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confidence: 99%

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Loss of Presynaptic Terminal Integrity in the Substantia Nigra in Early Parkinson's Disease

et al. 2020

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A BS TRACT: Background: It has been hypothesized that the pathology of Parkinson's disease (PD) primarily affects presynaptic terminals and spreads transsynaptically. Objectives: The main objective of this study was to assess the magnitude and anatomical extent of presynaptic terminal loss across the brain in early PD. A second objective was to compare loss of presynaptic terminals and cell bodies within the nigrostriatal tract. Methods: A total of 30 patients with early PD and 20 age-and gender-matched healthy controls underwent positron emission tomography with 11 C-UCB-J, a ligand for the universal presynaptic terminal marker synaptic vesicle protein 2A (SV2A), and with the dopamine transporter ligand 18 F-FE-PE2I, as well as a detailed clinical assessment. Volumes of interest were delineated based on individual 3-dimensional T1 magnetic resonance imaging. BP ND images were calculated. Results: Patients with PD showed significant loss of SV2A binding in the substantia nigra only. Loss of dopamine transporter binding in the PD group was much greater in the putamen than in the substantia nigra. We found no correlations between SV2A or dopamine transporter binding and any of the clinical motor or nonmotor scores. Homologous voxel-based analysis in the PD group showed significant correlations between SV2A and dopamine transporter binding in the caudate and substantia nigra. Conclusions: Presynaptic terminals appear to be the most heavily affected subcellular compartment of nigrostriatal neurons in early PD. Moreover, early PD causes loss of presynaptic terminals that innervate the nigrostriatal neurons. This loss of presynaptic boutons in the substantia nigra may reflect an axonal response to target deprivation or could possibly point to a transsynaptic mode of propagation of the disease process.

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Section: Discussionmentioning

confidence: 99%

Section: Image Acquisitionmentioning

confidence: 99%

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confidence: 99%

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Loss of Presynaptic Terminal Integrity in the Substantia Nigra in Early Parkinson's Disease

et al. 2020

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“…Nigrosome imaging [49,50] using T2* and susceptibility weighted imaging MRI sequences could be another SN MR-biomarker of interest to combine with DAT imaging. Further validation of the appropriate reference tissue and attenuation correction methods for DAT imaging with the new PET-MRI systems, however, is needed [38,[51][52][53].…”

Section: Pet-mrimentioning

confidence: 99%

Dopamine transporter imaging in neurodegenerative movement disorders: PET vs. SPECT

Kerstens

Varrone

2020

Clin Transl Imaging

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Purpose The dopamine transporter (DAT) serves as biomarker for parkinsonian syndromes. DAT can be measured in vivo with single-photon emission computed tomography (SPECT) and positron emission tomography (PET). DAT-SPECT is the current clinical molecular imaging standard. However, PET has advantages over SPECT measurements, and PET radioligands with the necessary properties for clinical applications are on the rise. Therefore, it is time to review the role of DAT imaging with SPECT compared to PET. Methods PubMed and Web of Science were searched for relevant literature of the previous 10 years. Four topics for comparison were used: diagnostic accuracy, quantitative accuracy, logistics, and flexibility. Results There are a few studies directly comparing DAT-PET and DAT-SPECT. PET and SPECT both perform well in discriminating neurodegenerative from non-neurodegenerative parkinsonism. Clinical DAT-PET imaging seems feasible only recently, thanks to simplified DAT assessments and better availability of PET radioligands and systems. The higher resolution of PET makes more comprehensive assessments of disease progression in the basal ganglia possible. Additionally, it has the possibility of multimodal target assessment. Conclusion DAT-SPECT is established for differentiating degenerative from non-degenerative parkinsonism. For further differentiation within neurodegenerative Parkinsonian syndromes, DAT-PET has essential benefits. Nowadays, because of wider availability of PET systems and radioligand production centers, and the possibility to use simplified quantification methods, DAT-PET imaging is feasible for clinical use. Therefore, DAT-PET needs to be considered for a more active role in the clinic to take a step forward to a more comprehensive understanding and assessment of Parkinson’s disease.

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“…Besides scan duration, the optimal time window for SBR estimation according to the [ 18 F]-FE-PE2I time activity curves is of particular interest: whereas first results proposed a static acquisition during the radioligands early peak equilibrium, 19 also image data of the late pseudo-equilibrium have been recently used 20 and recommended as more favourable for SBR estimation. 21 This study aims to expand on earlier SBR findings with a larger cohort of PD patients and control subjects and with two subgroups of PD patients, who underwent two [ 18 F]-FE-PE2I PET examinations to assess either test-retest reliability or longitudinal changes after a two-year follow-up. The purpose was to understand whether simplified quantification of DAT is more reliable during the early peak or the late pseudoequilibrium, and if a reduction of scan time to 18 min is feasible during early and late equilibrium.…”

Section: Introductionmentioning

confidence: 99%

Simplified quantification of [¹⁸F]FE-PE2I PET in Parkinson’s disease: Discriminative power, test–retest reliability and longitudinal validity during early peak and late pseudo-equilibrium

Brumberg

Kerstens

Cselényi

et al. 2020

J Cereb Blood Flow Metab

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Quantification of dopamine transporter (DAT) availability with [18F]FE-PE2I PET enables the detection of presynaptic dopamine deficiency and provides a potential progression marker for Parkinson`s disease (PD). Simplified quantification is feasible, but the time window of short acquisition protocols may have a substantial impact on the reliability of striatal binding estimates. Dynamic [18F]FE-PE2I PET data of cross-sectional (33 PD patients, 24 controls), test–retest (9 patients), and longitudinal (12 patients) cohorts were used to assess the variability and reliability of specific binding ratios (SBR) measured during early peak and late pseudo-equilibrium. Receiver operating characteristics area under the curve (PD vs. controls) was high for early (0.996) and late (0.991) SBR. Early SBR provided more favourable effect size, absolute variability, and standard error of measurement than late SBR (caudate: 1.29 vs. 1.23; 6.9% vs. 9.8%; 0.09 vs. 0.20; putamen: 1.75 vs. 1.67; 7.7% vs. 14.0%; 0.08 vs. 0.17). The annual percentage change was comparable for both time windows (−7.2%–8.5%), but decline was significant only for early SBR. Whereas early and late [18F]FE-PE2I PET acquisitions have similar discriminative power to separate PD patients and controls, the early peak equilibrium acquisition can be recommended if [18F]FE-PE2I is used to measure longitudinal changes of DAT availability.

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Quantification and discriminative power of 18F-FE-PE2I PET in patients with Parkinson’s disease

Cited by 27 publications

References 16 publications

Loss of Presynaptic Terminal Integrity in the Substantia Nigra in Early Parkinson's Disease

Loss of Presynaptic Terminal Integrity in the Substantia Nigra in Early Parkinson's Disease

Dopamine transporter imaging in neurodegenerative movement disorders: PET vs. SPECT

Simplified quantification of [¹⁸F]FE-PE2I PET in Parkinson’s disease: Discriminative power, test–retest reliability and longitudinal validity during early peak and late pseudo-equilibrium

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Quantification and discriminative power of 18F-FE-PE2I PET in patients with Parkinson’s disease

Cited by 27 publications

References 16 publications

Loss of Presynaptic Terminal Integrity in the Substantia Nigra in Early Parkinson's Disease

Loss of Presynaptic Terminal Integrity in the Substantia Nigra in Early Parkinson's Disease

Dopamine transporter imaging in neurodegenerative movement disorders: PET vs. SPECT

Simplified quantification of [18F]FE-PE2I PET in Parkinson’s disease: Discriminative power, test–retest reliability and longitudinal validity during early peak and late pseudo-equilibrium

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Simplified quantification of [¹⁸F]FE-PE2I PET in Parkinson’s disease: Discriminative power, test–retest reliability and longitudinal validity during early peak and late pseudo-equilibrium