Preclinical properties of 18F-AV-45: a PET agent for Abeta plaques in the brain.
Preclinical properties of 18F-AV-45: a PET agent for Abeta plaques in the brain.
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DOI：
10.2967/jnumed.109.065284
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发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
Kung HF
中科院分区：
文献类型：
--
作者：
Choi SR;Golding G;Zhuang Z;Zhang W;Lim N;Hefti F;Benedum TE;Kilbourn MR;Skovronsky D;Kung HF
大脑中的β-淀粉样斑块(Aβ斑块)，主要包含纤维状的Aβ多肽聚集体，代表了阿尔茨海默病(AD)的一个决定性的病理特征。靶向活体人脑Aβ斑块的显像剂作为AD发病过程的生物标志物具有潜在的价值。(E)-4-(2-(6-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl苯甲胺(18F-AV-45)是一种目前处于第三阶段临床研究的试剂，用于脑内Aβ斑块的正电子发射计算机断层扫描。用体外结合试验和放射自显影技术评价18F-AV-45与死后AD脑组织A-β斑块的体外结合。对18F-AV-45在小鼠体内的生物分布和AD转基因小鼠(APPSWE/PSEN1)脑内Aβ聚合体的体外放射自显影进行了研究。对静脉注射18F-AV-45后的猴脑进行了小动物正电子发射计算机断层扫描。18F-AV-45与A-β斑块具有较高的结合亲和力和特异性(Kd=3.72±0.30nM)。人死后大脑切片的体外放射自显影显示，AD大脑中有大量斑块标记，而对照组大脑中没有。观察到健康小鼠和猴子最初的脑摄取高和脑快速洗出。对健康小鼠静脉注射后血液中产生的代谢物进行了鉴定。体外放射自显影显示，18F-AV-45与转基因AD模型小鼠脑内Aβ斑块具有良好的结合亲和力。这些结果支持18F-AV-45可能是一种检测活体人脑Aβ斑块的有用的正电子发射计算机断层显像剂。
β-amyloid plaques (Aβ plaques) in the brain, containing predominantly fibrillary Aβ peptide aggregates, represent a defining pathologic feature of Alzheimer disease (AD). Imaging agents targeting the Aβ plaques in the living human brain are potentially valuable as biomarkers of pathogenesis processes in AD. (E)-4-(2-(6-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine (18F-AV-45) is such as an agent currently in phase III clinical studies for PET of Aβ plaques in the brain. In vitro binding of 18F-AV-45 to Aβ plaques in the postmortem AD brain tissue was evaluated by in vitro binding assay and autoradiography. In vivo biodistribution of 18F-AV-45 in mice and ex vivo autoradiography of AD transgenic mice (APPswe/PSEN1) with Aβ aggregates in the brain were performed. Small-animal PET of a monkey brain after an intravenous injection of 18F-AV-45 was evaluated. 18F-AV-45 displayed a high binding affinity and specificity to Aβ plaques (Kd, 3.72 ± 0.30 nM). In vitro autoradiography of postmortem human brain sections showed substantial plaque labeling in AD brains and not in the control brains. Initial high brain uptake and rapid washout from the brain of healthy mice and monkey were observed. Metabolites produced in the blood of healthy mice after an intravenous injection were identified. 18F-AV-45 displayed excellent binding affinity to Aβ plaques in the AD brain by ex vivo autoradiography in transgenic AD model mice. The results lend support that 18F-AV-45 may be a useful PET agent for detecting Aβ plaques in the living human brain.
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影响因子：
2.9
作者：
Kung, MP;Hou, C;Kung, HF
通讯作者：
Kung, HF
影响因子：
3.1
作者：
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2.1
作者：
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影响因子：
48
作者：
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通讯作者：
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影响因子：
11.2
作者：
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通讯作者：
Långström, B