18F-氟马西尼：γ-氨基丁酸 A 特异性 PET 放射性示踪剂，用于定位耐药性颞叶癫痫。

18F-flumazenil: a γ-aminobutyric acid A-specific PET radiotracer for the localization of drug-resistant temporal lobe epilepsy.

机构信息

Departments of Medicine and Neurology, Melbourne Brain Centre, The Royal Melbourne Hospital, University of Melbourne, Royal Parade, Parkville, Victoria, Australia.

出版信息

J Nucl Med. 2013 Aug;54(8):1270-7. doi: 10.2967/jnumed.112.107359. Epub 2013 Jul 15.

DOI:10.2967/jnumed.112.107359

PMID:23857513

Abstract

UNLABELLED

Studies report that (11)C-flumazenil (FMZ) PET more specifically localizes the epileptogenic zone in patients with medically refractory focal epilepsy than (18)F-FDG PET. However, practical aspects of (11)C use limit clinical application. We report a phase I/IIa study assessing the clinical use of (18)F-FMZ PET for the localization of the epileptogenic zone in patients with drug-resistant temporal lobe epilepsy (TLE). Receptor binding was quantified using kinetic modeling that did not require arterial sampling.

METHODS

Dynamic (18)F-FMZ PET and static interictal (18)F-FDG PET scans were compared in healthy controls (n = 17 for (18)F-FMZ and n = 20 for (18)F-FDG) and TLE patients with mesial temporal sclerosis on MR imaging (MTS, n = 12) and with normal MR imaging (NL TLE, n = 19). Masked visual assessment of images was undertaken. Parametric images of (18)F-FMZ binding potential (BPND) were generated using the simplified reference tissue model. Region-of-interest analysis on coregistered MR images and statistical parametric mapping were used to quantify (18)F-FMZ BPND and (18)F-FDG uptake in the temporal lobe.

RESULTS

The visual assessment of static standardized uptake value images showed (18)F-FMZ PET to have high specificity (16/17 [94%]) and moderate sensitivity (21/31 [68%]) for the localization of the epileptogenic zone, with a more restricted abnormality than (18)F-FDG PET. However, the (18)F-FMZ standardized uptake value images were falsely localizing in 3 of 31 patients (10%). Region-of-interest analysis demonstrated reductions in ipsilateral hippocampal (18)F-FMZ BPND in patients with either MTS or NL TLE, compared with controls subjects. Ipsilateral hippocampal (18)F-FMZ BPND was independent of both hippocampal volume and (18)F-FDG uptake, whereas ipsilateral hippocampal volume was correlated with (18)F-FDG uptake (r(2) = 0.69, P < 0.0001). Statistical parametric mapping analysis demonstrated decreased uptake in 14 of 31 (45%) cases with (18)F-FMZ PET and 18 of 29 (62%) with (18)F-FDG PET. Cluster size was significantly smaller on (18)F-FMZ than (18)F-FDG images (37 vs. 160 voxels, P < 0.01).

CONCLUSION

(18)F-FMZ PET has potential as a clinical tool for the localization of the epileptogenic zone in the presurgical evaluation of drug-resistant TLE, providing information complementary to (18)F-FDG PET, with a more restricted region of abnormality.

摘要

目的

研究报告称，与（18）F-FDG PET 相比，（11）C-flumazenil（FMZ）PET 更能特异性定位药物难治性局灶性癫痫患者的致痫区。然而，（11）C 的实际应用限制了其临床应用。我们报告了一项 I/IIa 期研究，评估了（18）F-FMZ PET 在药物难治性颞叶癫痫（TLE）患者致痫区定位中的临床应用。使用不需要动脉取样的动力学模型来量化受体结合。

方法

比较了健康对照组（（18）F-FMZ 为 17 例，（18）F-FDG 为 20 例）、磁共振成像（MRI）显示有内侧颞叶硬化（MTS）的 TLE 患者（n=12）和 MRI 正常的 TLE 患者（NL TLE，n=19）的动态（18）F-FMZ PET 和静态发作间期（18）F-FDG PET 扫描。进行了图像的掩蔽视觉评估。使用简化参考组织模型生成（18）F-FMZ 结合潜能（BPND）的参数图像。在配准的 MR 图像上进行感兴趣区分析和统计参数映射，以定量颞叶中的（18）F-FMZ BPND 和（18）F-FDG 摄取。

结果

静态标准化摄取值图像的视觉评估显示，（18）F-FMZ PET 对致痫区的定位具有较高的特异性（16/17 [94%]）和中等的敏感性（21/31 [68%]），其异常范围比（18）F-FDG PET 更局限。然而，（18）F-FMZ 标准化摄取值图像在 31 例患者中的 3 例（10%）中存在假定位。与对照组相比，无论是 MTS 还是 NL TLE 患者，对侧海马（18）F-FMZ BPND 均降低。对侧海马（18）F-FMZ BPND 与海马体积和（18）F-FDG 摄取均无关，而对侧海马体积与（18）F-FDG 摄取相关（r（2）=0.69，P<0.0001）。统计参数映射分析显示，14 例（45%）（18）F-FMZ PET 和 18 例（62%）（18）F-FDG PET 患者的摄取减少。（18）F-FMZ 图像上的簇大小明显小于（18）F-FDG 图像（37 个与 160 个体素，P<0.01）。