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 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 [ 18 F]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 [ 18 F]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: [ 18 F]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 [ 18 F]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 [ 18 F]FE-PE2I PET is a suitable marker for longitudinal DAT decline in PD.

[18F]FE-PE2I PET is a feasible alternative to [123I]FP-CIT SPECT for dopamine transporter imaging in clinically uncertain parkinsonism

“…In 2012, [ 18 F]FE-PE2I showed promising results in 10 healthy subjects [ 16 ] and this was substantiated by Shingai and co-workers [ 17 ] who found an age-related decline in DAT density of approximately 7.5% per decade in the caudate and putamen and 3.4% in substantia nigra. Reproducibility over time of PET measurements with [ 18 F]FE-PE2I demonstrated good agreement in twelve healthy male subjects[ 18 ] and later in nine PD patients [ 19 ], making [ 18 F]FE-PE2I PET feasible for studying long-term alterations in DAT availability. Based on dynamic [ 18 F]FE-PE2I PET scans in PD and healthy subjects, Sonni et al [ 20 ] suggested that static imaging during early peak (17–42 min after injection) could be used as a simplified quantification method compared to the full quantification using long dynamic acquisitions.…”

“…Several studies have investigated the use of [ 18 F]FE-PE2I in substantia nigra and report a less pronounced reduction of [ 18 F]FE-PE2I levels compared to striatum [ 22 – 24 ]. Repeatability and reliability have been shown to be very high in striatum with a variability of 5–7% and an intraclass coefficient of 0.91, but only modest in substantia nigra due to the smaller size and DAT density [ 19 ]. The effect size for discrimination between PD patients and healthy controls using [ 18 F]FE-PE2I PET as compared to [ 123 I]FP-CIT SPECT was found to be at least as good by Mo et al [ 25 ] in 22 presumed early-stage PD patients and 28 healthy controls.…”

Longitudinal DAT changes measured with [18F]FE-PE2I PET in patients with Parkinson’s disease; a validation study

“…The first cohort consists of twenty PD patients of which the baseline DAT PET data have already been reported ( Fazio et al, 2018 ). The second cohort consists of twenty PD patients of which the baseline PET of some were part of the previously reported test–retest study ( Kerstens et al, 2020 ).…”

“…This property was also confirmed in a subsequent healthy human PET study ( Fazio et al, 2015 ). Test-retest studies in healthy controls ( Suzuki et al, 2014 ) and non-advanced PD patients ( Kerstens et al, 2020 ) have shown good reliability and repeatability of [ 18 F]FE-PE2I PET measurements also in small or lower DAT density regions such as the substantia nigra. Recently, [ 18 F]FE-PE2I has also been included in the EANM guideline and SNMMI procedure standard for clinical DAT imaging in Parkinsonian syndromes ( Morbelli et al, 2020 )).…”

Mangosteen Pericarp Extract Supplementation Boosts Antioxidant Status via Rebuilding Gut Microbiota to Attenuate Motor Deficit in 6-OHDA-Induced Parkinson’s Disease

“…The imaging of DAT was used as a potential surrogate marker for dopaminergic neurons in nigrostriatal pathway. DAT mediates the transport of dopamine and DAT availability is restricted to dopaminergic neurons [ 41 , 42 ]. The analysis of DAT was conducted to further explain the observed motor function.…”