Translocator protein PET imaging in temporal lobe epilepsy: A reliable test-retest study using asymmetry index.
Translocator protein PET imaging in temporal lobe epilepsy: A reliable test-retest study using asymmetry index.
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DOI：
10.3389/fnimg.2023.1142463
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发表时间：
2023
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影响因子：
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通讯作者：
Johnson, Michael R
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作者：
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
转运蛋白（TSPO）靶向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的效用，可用于评估靶向神经炎症的新型疗法的疗效。然而，以前在健康志愿者中的研究表明TSPO配体的重测信度有限。在这里，我们使用TSPO PET成像检查癫痫受试者和健康对照者的重测措施，以探索这种生物标志物是否可以用作癫痫临床试验的终点。使用第二代TSPO靶向放射性配体[11 C] PBR 28，对5名癫痫并确诊内侧颞叶硬化的受试者（平均年龄36岁，3名男性）进行了两次扫描，平均间隔8周。我们评估了这些受试者中[11 C] PBR 28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了比较。所有受试者中，癫痫患者所有感兴趣区域（ROI）的测试和重新测试扫描的分布容积（VT）平均值（± SD）为4.49 ± 1.54，健康志愿者为5.89 ± 1.23。不对称指数的检验和重测之间的偏倚（以百分比表示）很小（-1.5%），此处使用Bland-Altman图证明了可靠性（检验均值1.062，重测均值2.56）。在癫痫受试者中，[11 C] PBR 28的VT在存在硬化的（同侧）海马区高于对侧区域。当使用TSPO PET在患有癫痫伴海马硬化（HS）的患者中时，海马中的半球间不对称指数是具有良好的重测信度的测量。我们提供了重测变异性的估计，这可能有助于估计功效，其中VT的组变化代表临床结局。
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, [11C]PBR28. We evaluated the test-retest reliability of the volume of distribution and derived hemispheric asymmetry index of [11C]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 (VT), 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, VT of [11C]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 VT represents the clinical outcome.