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

•[18F]FE-PE2I measures of DAT decline in PD agree with other radioligands.•It has, however, improved effect sizes for measuring intraindividual DAT changes.•Leading to lower needed sample sizes than routinely used [123I]FP-CIT.•Thus, this study validates its beneficial use in clinical, longitudinal...

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Published in:	NeuroImage clinical Vol. 37; p. 103347
Main Authors:	Kerstens, V.S., Fazio, P., Sundgren, M., Brumberg, J., Halldin, C., Svenningsson, P., Varrone, A.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Inc 2023 Elsevier
Subjects:	Aged Biomarker Caudate Nucleus - diagnostic imaging Caudate Nucleus - metabolism Dopamine Plasma Membrane Transport Proteins - metabolism Dopamine transporter Female Humans Longitudinal Male Medicin och hälsovetenskap Middle Aged Parkinson Disease - diagnostic imaging Parkinson’s disease Positron emission tomography Positron-Emission Tomography - methods Regular Reproducibility of Results Dopamine transporter Biomarker Longitudinal Positron emission tomography Parkinson’s disease
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Summary:	•[18F]FE-PE2I measures of DAT decline in PD agree with other radioligands.•It has, however, improved effect sizes for measuring intraindividual DAT changes.•Leading to lower needed sample sizes than routinely used [123I]FP-CIT.•Thus, this study validates its beneficial use in clinical, longitudinal PD studies. 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. To validate [18F]FE-PE2I PET as measurement tool of longitudinal DAT changes in patients with Parkinson’s disease. 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 (BPND) 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. 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2213-1582 2213-1582
DOI:	10.1016/j.nicl.2023.103347