Kerstens Vera S, Fazio Patrik, Sundgren Mathias, Matheson Granville J, Franzén Erika, Halldin Christer, Cervenka Simon, Svenningsson Per, Varrone Andrea
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, Stockholm, Sweden.
Department of Clinical Neuroscience, Division of Neuro, Karolinska Institutet, Stockholm, Sweden.
EJNMMI Res. 2020 Aug 14;10(1):95. doi: 10.1186/s13550-020-00676-4.
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 [F]FE-PE2I-PET in PD patients.
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 [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.
[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).
DAT-PET measurements with [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 [F]FE-PE2I PET is a suitable marker for longitudinal DAT decline in PD.
EudraCT 2017-003327-29.
可靠地定量多巴胺转运体（DAT），一种帕金森病（PD）的生物标志物，对于诊断目的以及评估潜在的疾病修饰治疗至关重要。由于多巴胺能神经元的退化，从而预期与DAT的放射性配体结合较低，因此预计PD患者的测量变异性会高于健康对照者早期的重复性结果。因此，我们旨在研究[F]FE-PE2I-PET在PD患者中的重测特性。
纳入9例PD患者（Hoehn和Yahr分期<3）（男性/女性6/3；平均年龄65.2±6.8岁）。每位患者在7 - 28天内进行两次[F]FE-PE2I-PET测量。结果指标是使用以小脑为参考区域的小波辅助参数成像生成的不可置换结合潜能。我们使用可靠性和重复性估计来评估重测性能。主要分析区域为尾状核、壳核、腹侧纹状体和黑质。对纹状体的功能亚区进行探索性分析。我们还比较了受累程度较轻与较重的一侧。
[F]FE-PE2I在纹状体区域的绝对变异性估计为5.3 - 7.6%，在黑质为11%，组内相关系数（ICC）为0.74 - 0.97（中位数0.91）。纹状体功能亚区的绝对变异性为6.0 - 9.6%，ICC为0.76 - 0.91（中位数0.91）。受累较轻的黑质比受累较重的一侧表现出更高的一致性。根据基于当前样本量的功效计算，纹状体中DAT变化5 - 11%以及黑质中变化28%时，功效为0.8（p < 0.0125）的变化可以被检测到。
PD患者使用[F]FE-PE2I进行DAT-PET测量显示出良好的重复性和可靠性。患者黑质中可靠性略低可能是由于DAT密度较低和解剖尺寸较小所致。功效计算表明，[F]FE-PE2I PET是PD中DAT纵向下降的合适标志物。
EudraCT 2017-003327-29。
