Clinical correlates of dopamine transporter availability in cross-sectional and longitudinal studies with [18F]FE-PE2I PET: independent validation with new insights.

IF 4.1 Q1 CLINICAL NEUROLOGY Brain communications Pub Date : 2024-10-02 eCollection Date: 2024-01-01 DOI:10.1093/braincomms/fcae345
Praveen Honhar, Faranak Ebrahimian Sadabad, Sule Tinaz, Jean-Dominique Gallezot, Mark Dias, Mika Naganawa, Yanghong Yang, Shannan Henry, Ansel T Hillmer, Hong Gao, Soheila Najafzadeh, Robert Comley, Nabeel Nabulsi, Yiyun Huang, Sjoerd J Finnema, Richard E Carson, David Matuskey
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Abstract

[18F]FE-PE2I PET is a promising alternative to single positron emission computed tomography-based dopamine transporter (DAT) imaging in Parkinson's disease. While the excellent discriminative power of [18F]FE-PE2I PET has been established, so far only one study has reported meaningful associations between motor severity scores and DAT availability. In this study, we use high-resolution (∼3 mm isotropic) PET to provide an independent validation for the clinical correlates of [18F]FE-PE2I imaging in separate cross-sectional (28 participants with Parkinson's disease, Hoehn-Yahr: 2 and 14 healthy individuals) and longitudinal (initial results from 6 participants with Parkinson's disease with 2-year follow-up) cohorts. In the cross-sectional cohort, DAT availability in the putamen and substantia nigra of patients with Parkinson's disease showed a significant negative association with total motor severity (r = -0.59, P = 0.002 for putamen; r = -0.46, P = 0.018 for substantia nigra), but not tremor severity. To our knowledge, this is the first observed association between motor severity in Parkinson's disease and DAT availability in the substantia nigra. The associations with motor severity in most nigrostriatal regions improved if tremor scores were excluded from motor scores. Further, we found significant asymmetry in DAT availability in the putamen (∼28% lower DAT availability within the more-affected side of the putamen), and DAT-based asymmetry index for the putamen was correlated with asymmetry in motor severity (r = -0.60, P = 0.001). In the longitudinal study, [18F]FE-PE2I PET detected significant annual percentage reduction of DAT availability at the individual level in the putamen (9.7 ± 2.6%), caudate (10.5 ± 3.8%) and ventral striatum (5.5 ± 2.7%), but not the substantia nigra. Longitudinal per cent reduction in DAT availability within the putamen was strongly associated with increase in motor severity (r = 0.91, P = 0.011) at follow-up, demonstrating the high sensitivity of [18F]FE-PE2I PET in tracking longitudinal changes. These results provide further evidence for the utility of [18F]FE-PE2I as an important in vivo PET biomarker in future clinical trials of Parkinson's disease.

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利用[18F]FE-PE2I PET 进行的横断面和纵向研究中多巴胺转运体可用性的临床相关性:独立验证与新见解。
[18F]FE-PE2I正电子发射计算机断层扫描是帕金森病中基于单一正电子发射计算机断层扫描的多巴胺转运体(DAT)成像的一种有前途的替代方法。虽然[18F]FE-PE2I PET 的卓越鉴别力已得到证实,但迄今为止只有一项研究报告了运动严重程度评分与 DAT 可用性之间有意义的关联。在本研究中,我们使用高分辨率(∼3 毫米各向同性)正电子发射计算机断层显像,在不同的横断面队列(28 名帕金森病患者,Hoehn-Yahr:2 和 14 名健康人)和纵向队列(6 名帕金森病患者的初步结果,随访 2 年)中对[18F]FE-PE2I 成像的临床相关性进行了独立验证。在横断面队列中,帕金森病患者的大脑丘脑和黑质中的DAT可用性与总运动严重程度呈显著负相关(大脑丘脑的相关系数为-0.59,P=0.002;黑质的相关系数为-0.46,P=0.018),但与震颤严重程度无关。据我们所知,这是首次观察到帕金森病的运动严重程度与黑质中DAT的可用性之间存在关联。如果将震颤评分从运动评分中剔除,则大多数黑质区域的运动严重程度的相关性会得到改善。此外,我们还发现,黑质中DAT的可用性存在明显的不对称性(黑质中受影响较重的一侧DAT可用性低28%),基于DAT的黑质不对称性指数与运动严重程度的不对称性存在相关性(r = -0.60,P = 0.001)。在纵向研究中,[18F]FE-PE2I PET检测到个体水平上的DAT可用性每年都有显著的百分比下降,如在普门(9.7 ± 2.6%)、尾状核(10.5 ± 3.8%)和腹侧纹状体(5.5 ± 2.7%),但在黑质却没有。在随访中,普塔门内DAT可用性的纵向百分比减少与运动严重性的增加密切相关(r = 0.91,P = 0.011),这表明[18F]FE-PE2I PET在追踪纵向变化方面具有很高的灵敏度。这些结果进一步证明了[18F]FE-PE2I作为一种重要的体内PET生物标记物在未来帕金森病临床试验中的实用性。
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