Reliability of dopamine transporter PET measurements with [18F]FE-PE2I in patients with Parkinson’s disease

Abstract Background Reliable quantification of dopamine transporter (DAT), a biomarker for Parkinson’s disease (PD), is essential for diagnostic purposes as well as for evaluation of potential disease-modifying treatment. Due to degeneration of dopaminergic neurons and thus lower expected radioligan...

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Main Authors: Vera S. Kerstens, Patrik Fazio, Mathias Sundgren, Granville J. Matheson, Erika Franzén, Christer Halldin, Simon Cervenka, Per Svenningsson, Andrea Varrone
Format: Article
Language:English
Published: SpringerOpen 2020-08-01
Series:EJNMMI Research
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Online Access:http://link.springer.com/article/10.1186/s13550-020-00676-4
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spelling doaj-816f37a01f1443e9814c904a3c1a7be62020-11-25T03:46:11ZengSpringerOpenEJNMMI Research2191-219X2020-08-011011910.1186/s13550-020-00676-4Reliability of dopamine transporter PET measurements with [18F]FE-PE2I in patients with Parkinson’s diseaseVera S. Kerstens0Patrik Fazio1Mathias Sundgren2Granville J. Matheson3Erika Franzén4Christer Halldin5Simon Cervenka6Per Svenningsson7Andrea Varrone8Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Karolinska University HospitalCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Karolinska University HospitalDepartment of Clinical Neuroscience, Division of Neuro, Karolinska InstitutetCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Karolinska University HospitalDepartment of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska InstitutetCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Karolinska University HospitalCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Karolinska University HospitalDepartment of Clinical Neuroscience, Division of Neuro, Karolinska InstitutetCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Karolinska University HospitalAbstract Background Reliable quantification of dopamine transporter (DAT), a biomarker for Parkinson’s disease (PD), is essential for diagnostic purposes as well as for evaluation of potential disease-modifying treatment. Due to degeneration of dopaminergic neurons and thus lower expected radioligand binding to DAT, higher measurement variability in PD patients might be expected than earlier reproducibility results in healthy controls. Therefore, we aimed to examine the test-retest properties of [18F]FE-PE2I-PET in PD patients. Methods Nine patients with PD (Hoehn and Yahr stage < 3) were included (men/women 6/3; mean age 65.2 ± 6.8 years). Each patient underwent two [18F]FE-PE2I-PET measurements within 7–28 days. The outcome measure was non-displaceable binding potential generated using wavelet-aided parametric imaging with cerebellum as reference region. We assessed test-retest performance using estimates of reliability and repeatability. Regions for primary analysis were caudate, putamen, ventral striatum, and substantia nigra. Exploratory analysis was performed for functional subdivisions of the striatum. We also compared the more vs. less affected side. Results [18F]FE-PE2I showed absolute variability estimates of 5.3–7.6% in striatal regions and 11% in substantia nigra and ICCs of 0.74–0.97 (median 0.91). The absolute variability for functional striatal subdivisions was 6.0–9.6% and ICCs of 0.76–0.91 (median 0.91). The less affected substantia nigra exhibited greater consistency than the more affected side. According to power calculations based on the current sample size, DAT changes of 5–11% in the striatum and 28% in the substantia nigra can be detected with a power of 0.8 (p < 0.0125). Conclusion DAT-PET measurements with [18F]FE-PE2I in PD patients showed good repeatability and reliability. The slightly lower reliability in the substantia nigra in patients may be explained by lower DAT density and smaller anatomical size. Power calculations suggest that [18F]FE-PE2I PET is a suitable marker for longitudinal DAT decline in PD. Trial registration EudraCT 2017-003327-29http://link.springer.com/article/10.1186/s13550-020-00676-4ReliabilityTest-retest[18F]FE-PE2IDopamine transporterParkinson’s disease
collection DOAJ
language English
format Article
sources DOAJ
author Vera S. Kerstens
Patrik Fazio
Mathias Sundgren
Granville J. Matheson
Erika Franzén
Christer Halldin
Simon Cervenka
Per Svenningsson
Andrea Varrone
spellingShingle Vera S. Kerstens
Patrik Fazio
Mathias Sundgren
Granville J. Matheson
Erika Franzén
Christer Halldin
Simon Cervenka
Per Svenningsson
Andrea Varrone
Reliability of dopamine transporter PET measurements with [18F]FE-PE2I in patients with Parkinson’s disease
EJNMMI Research
Reliability
Test-retest
[18F]FE-PE2I
Dopamine transporter
Parkinson’s disease
author_facet Vera S. Kerstens
Patrik Fazio
Mathias Sundgren
Granville J. Matheson
Erika Franzén
Christer Halldin
Simon Cervenka
Per Svenningsson
Andrea Varrone
author_sort Vera S. Kerstens
title Reliability of dopamine transporter PET measurements with [18F]FE-PE2I in patients with Parkinson’s disease
title_short Reliability of dopamine transporter PET measurements with [18F]FE-PE2I in patients with Parkinson’s disease
title_full Reliability of dopamine transporter PET measurements with [18F]FE-PE2I in patients with Parkinson’s disease
title_fullStr Reliability of dopamine transporter PET measurements with [18F]FE-PE2I in patients with Parkinson’s disease
title_full_unstemmed Reliability of dopamine transporter PET measurements with [18F]FE-PE2I in patients with Parkinson’s disease
title_sort reliability of dopamine transporter pet measurements with [18f]fe-pe2i in patients with parkinson’s disease
publisher SpringerOpen
series EJNMMI Research
issn 2191-219X
publishDate 2020-08-01
description Abstract Background Reliable quantification of dopamine transporter (DAT), a biomarker for Parkinson’s disease (PD), is essential for diagnostic purposes as well as for evaluation of potential disease-modifying treatment. Due to degeneration of dopaminergic neurons and thus lower expected radioligand binding to DAT, higher measurement variability in PD patients might be expected than earlier reproducibility results in healthy controls. Therefore, we aimed to examine the test-retest properties of [18F]FE-PE2I-PET in PD patients. Methods Nine patients with PD (Hoehn and Yahr stage < 3) were included (men/women 6/3; mean age 65.2 ± 6.8 years). Each patient underwent two [18F]FE-PE2I-PET measurements within 7–28 days. The outcome measure was non-displaceable binding potential generated using wavelet-aided parametric imaging with cerebellum as reference region. We assessed test-retest performance using estimates of reliability and repeatability. Regions for primary analysis were caudate, putamen, ventral striatum, and substantia nigra. Exploratory analysis was performed for functional subdivisions of the striatum. We also compared the more vs. less affected side. Results [18F]FE-PE2I showed absolute variability estimates of 5.3–7.6% in striatal regions and 11% in substantia nigra and ICCs of 0.74–0.97 (median 0.91). The absolute variability for functional striatal subdivisions was 6.0–9.6% and ICCs of 0.76–0.91 (median 0.91). The less affected substantia nigra exhibited greater consistency than the more affected side. According to power calculations based on the current sample size, DAT changes of 5–11% in the striatum and 28% in the substantia nigra can be detected with a power of 0.8 (p < 0.0125). Conclusion DAT-PET measurements with [18F]FE-PE2I in PD patients showed good repeatability and reliability. The slightly lower reliability in the substantia nigra in patients may be explained by lower DAT density and smaller anatomical size. Power calculations suggest that [18F]FE-PE2I PET is a suitable marker for longitudinal DAT decline in PD. Trial registration EudraCT 2017-003327-29
topic Reliability
Test-retest
[18F]FE-PE2I
Dopamine transporter
Parkinson’s disease
url http://link.springer.com/article/10.1186/s13550-020-00676-4
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