Dataset Information

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

ABSTRACT:

Background

Dopamine transporter (DAT) PET provides higher resolution than DAT SPECT and opportunity for integrated imaging with MRI. The radioligand [¹⁸F]FE-PE2I is highly selective for the DAT, and PET measurements with this radioligand have good reliability and repeatability in patients with non-advanced Parkinson's disease.

Objectives

To validate [¹⁸F]FE-PE2I PET as measurement tool of longitudinal DAT changes in patients with Parkinson's disease.

Methods

Thirty-seven subjects with Parkinson's disease (Hoehn and Yahr stage < 3) were included in a longitudinal PET study with [¹⁸F]FE-PE2I. DAT availability (BP_ND) in the caudate nucleus, putamen, sensorimotor striatum, and substantia nigra, was estimated with parametric imaging using Logan graphical analysis and cerebellum as reference region. For comparison with DAT-SPECT literature, sample size calculations for disease intervention studies were made.

Results

Baseline and follow-up PET data (interval: 2.3 ± 0.5 years) were available for 25 patients (9 females, 16 males). Median age was 64.7 years (range 46-76); symptom duration: 3 years (0.25-14); Hoehn and Yahr stage (H&Y): 1 (1-2). Annualized DAT decline and effect size were: -8.5 ± 6.6 % and 1.08 for caudate nucleus; -7.1 ± 6.1 % and 1.02 for putamen; -8.3 ± 8.5 % and 0.99 for sensorimotor striatum; -0.11 ± 9.3 % and 0.11 for substantia nigra. The estimated minimum sample size needed for a treatment trial using [¹⁸F]FE-PE2I PET as imaging marker is 2-3 times lower than is reported in literature on [¹²³I]FP-CIT SPECT.

Conclusions

Longitudinal [¹⁸F]FE-PE2I PET measurements in non-advanced PD demonstrate a striatal DAT decline consistent with previous SPECT and PET studies. No obvious changes of DAT availability were observed in the substantia nigra, indicating perhaps slower progression or compensatory changes. The effect sizes were numerically larger than reported in the literature for other DAT radioligands, suggesting that [¹⁸F]FE-PE2I might detect smaller DAT changes, and can be well used as progression marker in clinical trials.

SUBMITTER: Kerstens VS

PROVIDER: S-EPMC9978841 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Longitudinal DAT changes measured with [<sup>18</sup>F]FE-PE2I PET in patients with Parkinson's disease; a validation study.

Kerstens V S VS Fazio P P Sundgren M M Brumberg J J Halldin C C Svenningsson P P Varrone A A

NeuroImage. Clinical 20230211

<h4>Background</h4>Dopamine transporter (DAT) PET provides higher resolution than DAT SPECT and opportunity for integrated imaging with MRI. The radioligand [<sup>18</sup>F]FE-PE2I is highly selective for the DAT, and PET measurements with this radioligand have good reliability and repeatability in patients with non-advanced Parkinson's disease.<h4>Objectives</h4>To validate [<sup>18</sup>F]FE-PE2I PET as measurement tool of longitudinal DAT changes in patients with Parkinson's disease.<h4>Metho ...[more]

PMID: 36822016

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Project description: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.

Project description:[18F]FE-PE2I PET is a promising alternative to single positron emission computed tomography-based dopamine transporter (DAT) imaging in Parkinson's disease. While the excellent discriminative power of [18F]FE-PE2I PET has been established, so far only one study has reported meaningful associations between motor severity scores and DAT availability. In this study, we use high-resolution (∼3 mm isotropic) PET to provide an independent validation for the clinical correlates of [18F]FE-PE2I imaging in separate cross-sectional (28 participants with Parkinson's disease, Hoehn-Yahr: 2 and 14 healthy individuals) and longitudinal (initial results from 6 participants with Parkinson's disease with 2-year follow-up) cohorts. In the cross-sectional cohort, DAT availability in the putamen and substantia nigra of patients with Parkinson's disease showed a significant negative association with total motor severity (r = -0.59, P = 0.002 for putamen; r = -0.46, P = 0.018 for substantia nigra), but not tremor severity. To our knowledge, this is the first observed association between motor severity in Parkinson's disease and DAT availability in the substantia nigra. The associations with motor severity in most nigrostriatal regions improved if tremor scores were excluded from motor scores. Further, we found significant asymmetry in DAT availability in the putamen (∼28% lower DAT availability within the more-affected side of the putamen), and DAT-based asymmetry index for the putamen was correlated with asymmetry in motor severity (r = -0.60, P = 0.001). In the longitudinal study, [18F]FE-PE2I PET detected significant annual percentage reduction of DAT availability at the individual level in the putamen (9.7 ± 2.6%), caudate (10.5 ± 3.8%) and ventral striatum (5.5 ± 2.7%), but not the substantia nigra. Longitudinal per cent reduction in DAT availability within the putamen was strongly associated with increase in motor severity (r = 0.91, P = 0.011) at follow-up, demonstrating the high sensitivity of [18F]FE-PE2I PET in tracking longitudinal changes. These results provide further evidence for the utility of [18F]FE-PE2I as an important in vivo PET biomarker in future clinical trials of Parkinson's disease.

Project description:BackgroundDopamine transporter (DAT) imaging is used in the diagnostic work-up in suspected parkinsonian syndromes and dementia with Lewy bodies but cannot differentiate between these syndromes, and an extra brain imaging examination of the regional cerebral blood flow (rCBF) or glucose metabolism is often needed for differential diagnosis. The requirement of two different imaging examinations is resource-consuming and inconvenient for the patients. Therefore, imaging of both cortical blood flow and DAT imaging with the same radiotracer would be more convenient and cost-effective. The aim of this study was to test whether relative regional cerebral blood flow (rCBFR) can be measured with the DAT-specific positron emission tomography (PET) tracer [18F]FE-PE2I (FE-PE2I), by validation with cerebral perfusion measured with [15O]H2O PET (H2O).MethodsThe rCBFR was quantified by kinetic modeling for FE-PE2I (R1) and H2O (F). The R1 was calculated using the simplified reference tissue model, and F was calculated with a modified Koopman double-integration method. The linear relationship and intraclass correlation (ICC) between R1 and F were tested in image data derived from 29 patients with recent onset parkinsonism and 30 healthy controls.ResultsThere was a strong linear correlation across all subjects between R1 and F in the frontal, parietal, temporal, cingulate and occipital cortex as well as in the striatum (r ≥ 0.731-0.905, p < 0.001) with a good-to-excellent ICC, ranging from 0.727 to 0.943 (p < 0.001).ConclusionsOur results suggest that FE-PE2I may be used as a proxy for cerebral perfusion, thus potentially serving as a radiotracer for assessment of both DAT availability and rCBFR in one single dynamic scan. This could be valuable in the differential diagnosis of parkinsonian syndromes.Trial registrationEUDRA-CT 2015-003045-26. Registered 23 October 2015 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-003045-26.

Dataset Information

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

Background

Objectives

Methods

Results

Conclusions

Publications

Longitudinal DAT changes measured with [<sup>18</sup>F]FE-PE2I PET in patients with Parkinson's disease; a validation study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background

Objectives

Methods

Results

Conclusions

Publications

Longitudinal DAT changes measured with [<sup>18</sup>F]FE-PE2I PET in patients with Parkinson's disease; a validation study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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