18F-THK5351 tau tracer Alzheimer’s disease Monoamine oxidase-B Positron emission tomography Selegiline
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摘要

BACKGROUND:18F-THK5351 is a quinoline-derived tau imaging agent with high affinity to paired helical filaments (PHF). However, high levels of 18F-THK5351 retention in brain regions thought to contain negligible concentrations of PHF raise questions about the interpretation of the positron emission tomography (PET) signals, particularly given previously described interactions between quinolone derivatives and monoamine oxidase B (MAO-B). Here, we tested the effects of MAO-B inhibition on 18F-THK5351 brain uptake using PET and autoradiography.
METHODS:Eight participants (five mild cognitive impairment, two Alzheimer's disease, and one progressive supranuclear palsy) had baseline 18F-AZD4694 and 18F-THK5351 scans in order to quantify brain amyloid and PHF load, respectively. A second 18F-THK5351 scan was conducted 1 week later, 1 h after a 10-mg oral dose of selegiline. Three out of eight patients also had a third 18F-THK5351 scan 9-28 days after the selegiline administration. The primary outcome measure was standardized uptake value (SUV), calculated using tissue radioactivity concentration from 50 to 70 min after 18F-THK5351 injection, normalizing for body weight and injected radioactivity. The SUV ratio (SUVR) was determined using the cerebellar cortex as the reference region. 18F-THK5351 competition autoradiography studies in postmortem tissue were conducted using 150 and 500 nM selegiline.
RESULTS:At baseline, 18F-THK5351 SUVs were highest in the basal ganglia (0.64 ± 0.11) and thalamus (0.62 ± 0.14). In the post-selegiline scans, the regional SUVs were reduced on average by 36.7% to 51.8%, with the greatest reduction noted in the thalamus (51.8%) and basal ganglia (51.4%). MAO-B inhibition also reduced 18F-THK5351 SUVs in the cerebellar cortex (41.6%). The SUVs remained reduced in the three patients imaged at 9-28 days. Tissue autoradiography confirmed the effects of MAO-B inhibition on 18F-THK5351 uptake.
CONCLUSIONS:These results indicate that the interpretation of 18F-THK5351 PET images, with respect to tau, is confounded by the high MAO-B availability across the entire brain. In addition, the heterogeneous MAO-B availability across the cortex may limit the interpretation of 18F-THK5351 scans using reference region methods.

译文

背景: 18F-THK5351 是一种喹啉衍生的 tau 显像剂,对配对螺旋丝 (PHF) 具有高亲和力。然而,被认为含有可忽略的 PHF 浓度的大脑区域中 18F-THK5351 的高水平滞留引发了关于正电子发射断层扫描 (PET) 信号解释的问题, 特别给出了先前描述的喹诺酮衍生物和单胺氧化酶 B (MAO-B) 之间的相互作用。在这里,我们使用 PET 和放射自显影术测试了 MAO-B 抑制对 18F-THK5351 脑摄取的影响。
方法: 8 名参与者 (5 名轻度认知障碍、 2 名阿尔茨海默病和 1 名进行性核上性麻痹) 分别进行基线 18F-AZD4694 和 18F-THK5351 扫描,以量化大脑淀粉样蛋白和 PHF 负荷。1 周后进行第二次 18F-THK5351 扫描,1 小时后口服 10-mg 司来吉兰。八个患者中有三个在给药后 9-28 天进行了第三次 18F-THK5351 扫描。主要结果测量是标准化摄取值 (SUV),使用 18F-THK5351 注射后 50 至 70 分钟的组织放射性浓度计算,体重正常化和注射放射性。使用小脑皮质作为参考区域确定 SUV 比率 (SUVR)。使用 150 和 500 纳米的司来吉兰在死后组织中进行 18F-THK5351 竞争放射自显影研究。
结果: 基线时,基底神经节 (0.64 ± 0.11) 和丘脑 (0.62 ± 0.14) 的 18f-thc5351 suv 最高。在 selegiline 扫描后,区域 suv 平均减少了 36.7% 到 51.8%,最大的减少发生在丘脑 (51.8%) 和基底节 (51.4%)。MAO-B 抑制也减少了小脑皮质的 18F-THK5351 suv (41.6%)。三个病人在 9-28 天的成像中,越野车仍然减少。组织放射自显影证实了 MAO-B 抑制对 18F-THK5351 摄取的影响。
结论: 这些结果表明,18F-THK5351 PET 图像关于 tau 的解释被整个大脑的高 MAO-B 可用性所混淆。此外,跨皮层的异质 MAO-B 的可用性可能会限制使用参考区域方法对 18F-THK5351 扫描的解释。

Monoamine Oxidase

消化 肝纤维化 临床研究术语
概述  :  

单胺氧化酶(monoamine oxidase,MAO)为反映肝纤维化的酶,可分为两类。一类存在于肝、肾等组织的线粒体中,以FAD为辅酶,参与儿茶酚胺的分解代谢。另一类存在于结缔组织,是一种细胞外酶,无FAD而含有磷酸吡哆醛,只对伯胺起作用。血清中MAO和结缔组织中的MAO性质相似,能促进结缔组织的成熟,参与胶原成熟最后阶段架桥形成,使胶原与弹性硬蛋白结合。广泛分布于肝、肾、胃、小肠和脑等组织。肝脏MAO存在于线粒体中,少量存在于细胞质可溶成分中。 检测方法比色法与速率法(多用)。

monoamine 英 [,mɒnəʊ'eɪmiːn]

释义   n. [有化] 一元胺;单胺,单胺类

例句   Objective: To study the effect of subhypothermia and hypoxia on the contents of brain monoamine neurotransmitters and serum electrolyte. 目的:研究亚低温低压缺氧对大鼠脑单胺类神经递质含量和血清电解质水平的影响。

 

oxidase 英 ['ɒksɪdeɪz]

释义   n. [生化] 氧化酶

例句   Glucose oxidase consumes oxygen in the process of glucose oxidation. 葡萄糖氧化酶在氧化葡萄糖的过程中消耗氧。


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