Measuring Dopamine Transporter Availability and Synaptic Density in Parkinson's Disease: A Dual-Tracer Positron Emission Tomography Imaging Study.

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2025-10-03 DOI:10.1002/mds.70041

Faranak Ebrahimian Sadabad,Tommaso Volpi,Praveen Honhar,Sule Tinaz,Mark Dias,Takuya Toyonaga,Mika Naganawa,Jean-Dominique Gallezot,Yanghong Yang,Waleed Ibrahim,Brian Pittman,Salih Cayir,Rajiv Radhakrishnan,Gustavo A Angarita,Sophie E Holmes,Robert Comley,Richard E Carson,Sjoerd J Finnema,David Matuskey

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引用次数: 0

Abstract

BACKGROUND 18F-FE-PE2I is a highly selective dopamine transporter (DAT) positron emission tomography (PET) radioligand, whereas 11C-UCB-J targets synaptic vesicle glycoprotein 2A (SV2A), enabling the assessment of synaptic density. Both tracers show significant alterations in Parkinson's disease (PD) in nigrostriatal regions. However, the extent of overlap between overall synaptic loss and dopaminergic denervation across different disease stages remains unclear. OBJECTIVE To evaluate similarities and differences between patterns of DAT and SV2A binding in healthy controls (HC) and PD patients at different disease stages. METHODS Thirty patients with PD (12 women, age: 65.8 ± 7.1 years) and thirteen HCs (7 women, age: 57.8 ± 5.4 years) underwent PET imaging with 18F-FE-PE2I and 11C-UCB-J on separate days. Patients with PD were also stratified by disease duration into two subgroups (<3 years, n = 10; >6 years, n = 11). Binding potentials (BPND) were quantified in four regions of interest (ROIs): caudate, putamen, ventral striatum (VS), and substantia nigra (SN). Between-group differences in BPND were evaluated against HCs for each tracer, and correlations between 18F-FE-PE2I and 11C-UCB-J BPND were evaluated. RESULTS In HCs, significant correlations were observed between caudate 18F-FE-PE2I and striatal 11C-UCB-J BPND (caudate, putamen, VS). In PD (full cohort and longer-duration subgroup), significant correlations emerged between SN 11C-UCB-J and striatal 18F-FE-PE2I. Percent differences between patients with PD and HCs with 18F-FE-PE2I and 11C-UCB-J were similar only in the SN. CONCLUSIONS This study examined the relationship between DAT and overall synaptic density in nigrostriatal ROIs in PD using dual-tracer PET imaging, and there were distinct patterns that vary across disease stages. Understanding the interplay between dopaminergic and presynaptic degeneration in PD could enhance our knowledge of its pathophysiology and contribute to improve diagnosis. © 2025 International Parkinson and Movement Disorder Society.

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测量帕金森病多巴胺转运体可用性和突触密度：双示踪正电子发射断层成像研究。

背景：18f - fe - pe2i是一种高度选择性的多巴胺转运体（DAT）正电子发射断层扫描（PET）放射配体，而11C-UCB-J靶向突触囊泡糖蛋白2A (SV2A)，从而能够评估突触密度。两种示踪剂均显示帕金森病（PD）黑质纹状体区域的显著改变。然而，在不同的疾病阶段，总的突触丧失和多巴胺能去神经支配之间的重叠程度仍不清楚。目的探讨健康对照（HC）和PD患者不同疾病阶段DAT和SV2A结合模式的异同。方法30例PD患者（女性12例，年龄65.8±7.1岁）和13例hc患者（女性7例，年龄57.8±5.4岁）分别于隔天采用18F-FE-PE2I和11C-UCB-J进行PET显像。PD患者也按病程分为两个亚组（6年，n = 11）。在尾状体、壳核、腹侧纹状体和黑质四个感兴趣区域（roi）量化结合电位（BPND）。对每种示踪剂的HCs评估BPND的组间差异，并评估18F-FE-PE2I和11C-UCB-J BPND之间的相关性。结果在hc中，尾状体18F-FE-PE2I与纹状体11C-UCB-J BPND（尾状体、壳核、VS）呈显著相关。在PD（全队列和长期亚组）中，SN 11C-UCB-J与纹状体18F-FE-PE2I之间存在显著相关性。PD患者和hc患者携带18F-FE-PE2I和11C-UCB-J的百分比差异仅在SN中相似。结论本研究通过双示踪PET成像检测PD黑质纹状体ROIs中DAT与总突触密度之间的关系，并且在不同的疾病阶段存在不同的模式。了解多巴胺能与PD突触前变性之间的相互作用，有助于提高我们对PD病理生理学的认识，并有助于提高PD的诊断水平。©2025国际帕金森和运动障碍学会。

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.