Mahmud Mohammad, Wade Charles, Jawad Sarah, Hadi Zaeem, Otoul Christian, Kaminski Rafal M, Muglia Pierandrea, Kadiu Irena, Rabiner Eugenii, Maguire Paul, Owen David R, Johnson Michael R
Department of Brain Sciences, Imperial College London, London, United Kingdom.
Clinical Imaging Translational, UCB Pharma SA, Brussels, Belgium.
Front Neuroimaging. 2023 Apr 28;2:1142463. doi: 10.3389/fnimg.2023.1142463. eCollection 2023.
Translocator protein (TSPO) targeting positron emission tomography (PET) imaging radioligands have potential utility in epilepsy to assess the efficacy of novel therapeutics for targeting neuroinflammation. However, previous studies in healthy volunteers have indicated limited test-retest reliability of TSPO ligands. Here, we examine test-retest measures using TSPO PET imaging in subjects with epilepsy and healthy controls, to explore whether this biomarker can be used as an endpoint in clinical trials for epilepsy.
Five subjects with epilepsy and confirmed mesial temporal lobe sclerosis (mean age 36 years, 3 men) were scanned twice-on average 8 weeks apart-using a second generation TSPO targeting radioligand, [C]PBR28. We evaluated the test-retest reliability of the volume of distribution and derived hemispheric asymmetry index of [C]PBR28 binding in these subjects and compared the results with 8 (mean age 45, 6 men) previously studied healthy volunteers.
The mean (± SD) of the volume of distribution (), of all subjects, in patients living with epilepsy for both test and retest scans on all regions of interest (ROI) is 4.49 ± 1.54 vs. 5.89 ± 1.23 in healthy volunteers. The bias between test and retest in an asymmetry index as a percentage was small (-1.5%), and reliability is demonstrated here with Bland-Altman Plots (test mean 1.062, retest mean 2.56). In subjects with epilepsy, of [C]PBR28 is higher in the (ipsilateral) hippocampal region where sclerosis is present than in the contralateral region.
When using TSPO PET in patients with epilepsy with hippocampal sclerosis (HS), an inter-hemispheric asymmetry index in the hippocampus is a measure with good test-retest reliability. We provide estimates of test-retest variability that may be useful for estimating power where group change in represents the clinical outcome.
靶向转运蛋白（TSPO）的正电子发射断层扫描（PET）成像放射性配体在癫痫中具有潜在应用价值，可用于评估针对神经炎症的新型疗法的疗效。然而，先前在健康志愿者中的研究表明，TSPO配体的重测信度有限。在此，我们在癫痫患者和健康对照中使用TSPO PET成像检查重测指标，以探讨该生物标志物是否可作为癫痫临床试验的一个终点。
5例确诊为内侧颞叶硬化的癫痫患者（平均年龄36岁，3名男性）使用第二代靶向TSPO的放射性配体[C]PBR28进行两次扫描，平均间隔8周。我们评估了这些受试者中[C]PBR28结合的分布容积和半球不对称指数的重测信度，并将结果与8名（平均年龄45岁，6名男性）先前研究的健康志愿者进行比较。
所有受试者在癫痫患者中，所有感兴趣区域（ROI）的测试和重测扫描中分布容积（）的平均值（±标准差）为4.49±1.54，而健康志愿者为5.89±1.23。不对称指数作为百分比的测试和重测之间的偏差很小（-1.5%），Bland-Altman图显示了重测信度（测试平均值1.062，重测平均值2.56）。在癫痫患者中，存在硬化的（同侧）海马区[C]PBR28的 高于对侧区域。
在海马硬化（HS）的癫痫患者中使用TSPO PET时，海马的半球间不对称指数是一种具有良好重测信度的测量方法。我们提供了重测变异性的估计值，这可能有助于在 的组变化代表临床结果时估计检验效能。
