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 [18F]FE-PE2I-PET in PD patients. Methods. Nine patients with PD (Hoehn & Yahr stage < 3) were included (men/women: 6/3; mean age 65.2±6.8y). 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 number: EudraCT 2017-003327-29