[11C](R)-PK11195 positron emission tomography imaging of activated microglia in vivo in Rasmussen's encephalitis

[11C](R)-PK11195 positron emission tomography imaging of activated microglia in vivo in Rasmussen's encephalitis
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DOI:
10.1212/wnl.53.9.2199
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发表时间:
1999-12-10
期刊:
影响因子:
9.9
通讯作者:
Duncan, JS
Duncan, JS
中科院分区:
医学1区
文献类型:
--
作者:
Banati, RB;Goerres, GW;Duncan, JS

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本研究旨在探索使用[C-11](R)-PK 11195作为活化小胶质细胞/脑巨噬细胞的体内标记物进行PET评估拉斯穆森脑炎(RE)中神经炎症的可行性。[C-11](R)-PK 11195 PET在4名正常受试者、2名组织学证实的RE患者和3名临床稳定的海马硬化和低癫痫发作频率患者中进行。生成每例受试者的结合电位图,显示[C-11](R)-PR 11195的特异性结合。在配准和空间转换到受试者自己的MRI后,计算解剖学定义的感兴趣区域的区域结合电位值。在一名接受大脑半球切除术的RE患者中,切除的石蜡包埋的脑组织用标记活化的人类小胶质细胞的抗体(CR 3/43)染色。尽管临床稳定的海马硬化中[C-11](R)-PK 11195的特异性结合与正常脑中的相似,但RE患者在整个受累半球中显示出局灶性和弥漫性结合增加。在RE中,[11 C](R)-PK 11195 PET可以在体内显示死后神经病理学研究中已知的特征性单侧模式。激活的小胶质细胞/脑巨噬细胞的PET成像提供了一种工具,用于调查一系列脑疾病,其中神经炎症是一个组成部分,其中常规MRI不能明确指示炎症组织反应。[C-11](R)-PK 11195 PET可能有助于选择适当的活检部位,并进一步评估缓解乳腺癌疾病治疗的疗效。
This study was designed to explore the feasibility of PET using [C-11](R)-PK11195 as an in vivo marker of activated microglia/brain macrophages for the assessment of neuroinflammation in Rasmussen's encephalitis (RE). [C-11](R)-PK11195 PET was carried out in four normal subjects, two patients with histologically confirmed RE, and three patients with clinically stable hippocampal sclerosis and low seizure frequency. Binding potential maps showing specific binding of [C-11](R)-PR11195 were generated for each subject. Regional binding potential values were calculated for anatomically defined regions of interest after coregistration to and spatial transformation into the subjects' own MRI. In one patient with RE who underwent hemispherectomy, the resected, paraffin-embedded brain tissue was stained with an antibody (CR3/43) that labels activated human microglia. Whereas specific binding of [C-11](R)-PK11195 in clinically stable hippocampal sclerosis was similar to that in normal brain, patients with RE showed a focal and diffuse increase in binding throughout the affected hemisphere. in RE, [11C](R)-PK11195 PET can reveal in vivo the characteristic, unilateral pattern known from postmortem neuropathologic study. PET imaging of activated microglia/brain macrophages offers a tool for investigation of a range of brain diseases where neuroinflammation is a component and in which conventional MRI does not unequivocally indicate an inflammatory tissue reaction. [C-11](R)-PK11195 PET may help in the choice of appropriate biopsy sites and, further, may allow assessment of the efficacy of antiinflammatory disease-modifying treatment.