Juri Carlos, Kramer Vasko, Riss Patrick J, Soza-Ried Cristian, Haeger Arlette, Pruzzo Rossana, Rösch Frank, Amaral Horacio, Chana-Cuevas Pedro
Department of Chemistry, University of Oslo, Oslo, Norway.
Positronpharma SA, Santiago, Chile.
Clin Nucl Med. 2021 Feb 1;46(2):119-124. doi: 10.1097/RLU.0000000000003430.
Degeneration of dopaminergic, nigrostriatal neurons is the hallmark of Parkinson disease (PD), and PET quantification of dopamine transporters is a widely accepted method for differential diagnosis between idiopathic PD and essential tremor. [18F]PR04.MZ is a new PET tracer with excellent imaging properties allowing for precise quantification of striatal and extrastriatal dopamine transporter. Here we describe our initial experience with [18F]PR04.MZ PET/CT in a larger cohort of healthy controls and PD patients as a proof-of-concept study for this tracer.
Eighteen healthy subjects, 19 early PD patients (Hoehn-Yahr I-II), and 13 moderate-advanced PD patients (Hoehn-Yahr III-IV) underwent static PET/CT scans 60 to 90 minutes after injection of 5.16 ± 1.03 mCi (191 ± 38 MBq) [18F]PR04.MZ. Specific binding ratios (SBRs) were calculated for caudate nucleus, anterior putamen, posterior putamen, substantia nigra (SNpc), compared between different groups and correlated with clinical ratings.
[18F]PR04.MZ showed very high and specific uptake in the putamen, caudate, and substantia nigra pars compacta and very low nonspecific binding in other brain regions, and SBR values for the control group were 22.3 ± 4.1, 19.1 ± 3.5, and 5.4 ± 1.2, respectively. A reduction of SBR values was observed in all regions and in both initial and moderate PD, ranging from 35% to 89% (P < 0.001). The observed pattern of reduction was posterior putamen > anterior putamen > substantia nigra pars compacta > caudate, with contralateral posterior putamen being the most affected region. Rostrocaudal depletion gradient was evident in all PD patients and progression correlated with motor manifestations.
[18F]PR04.MZ PET/CT is a highly sensitive imaging modality for the detection of dopaminergic deficit in nigrostriatal pathways in PD.
多巴胺能黑质纹状体神经元变性是帕金森病(PD)的标志,多巴胺转运体的PET定量分析是鉴别特发性PD和特发性震颤的一种广泛接受的方法。[18F]PR04.MZ是一种新型PET示踪剂,具有出色的成像特性,可对纹状体和纹状体以外的多巴胺转运体进行精确量化。在此,我们描述了在更大规模的健康对照者和PD患者队列中使用[18F]PR04.MZ PET/CT的初步经验,作为该示踪剂的概念验证研究。
18名健康受试者、19名早期PD患者(Hoehn-Yahr I-II期)和13名中晚期PD患者(Hoehn-Yahr III-IV期)在注射5.16±1.03 mCi(191±38 MBq)[18F]PR04.MZ后60至90分钟接受静态PET/CT扫描。计算尾状核、壳核前部、壳核后部、黑质致密部(SNpc)的特异性结合率(SBR),比较不同组之间的差异,并与临床评分相关联。
[18F]PR04.MZ在壳核、尾状核和黑质致密部显示出非常高的特异性摄取,在其他脑区的非特异性结合非常低,对照组的SBR值分别为22.3±4.1、19.1±3.5和5.4±1.2。在所有区域以及早期和中期PD患者中均观察到SBR值降低,范围为35%至89%(P<0.001)。观察到的降低模式为壳核后部>壳核前部>黑质致密部>尾状核,对侧壳核后部是受影响最严重的区域。在所有PD患者中均存在明显的头尾侧耗竭梯度,且进展与运动表现相关。
[18F]PR04.MZ PET/CT是检测PD患者黑质纹状体通路多巴胺能缺陷的一种高度敏感的成像方式。