使用放射性配体 18F-AV-45（florbetapir [校正] F 18）对阿尔茨海默病中的淀粉样蛋白沉积进行体内成像。

In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18).

机构信息

Division of Nuclear Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-0807, USA.

出版信息

J Nucl Med. 2010 Jun;51(6):913-20. doi: 10.2967/jnumed.109.069088.

DOI:10.2967/jnumed.109.069088

PMID:20501908

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3101877/

Abstract

UNLABELLED

An (18)F-labeled PET amyloid-beta (Abeta) imaging agent could facilitate the clinical evaluation of late-life cognitive impairment by providing an objective measure for Alzheimer disease (AD) pathology. Here we present the results of a clinical trial with (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine ((18)F-AV-45 or florbetapir [corrected] F 18).

METHODS

An open-label, multicenter brain imaging, metabolism, and safety study of (18)F-AV-45 was performed on 16 patients with AD (Mini-Mental State Examination score, 19.3 +/- 3.1; mean age +/- SD, 75.8 +/- 9.2 y) and 16 cognitively healthy controls (HCs) (Mini-Mental State Examination score, 29.8 +/- 0.45; mean age +/- SD, 72.5 +/- 11.6 y). Dynamic PET was performed over a period of approximately 90 min after injection of the tracer (370 MBq [10 mCi]). Standardized uptake values and cortical-to-cerebellum standardized uptake value ratios (SUVRs) were calculated. A simplified reference tissue method was used to generate distribution volume ratio (DVR) parametric maps for a subset of subjects.

RESULTS

Valid PET data were available for 11 AD patients and 15 HCs. (18)F-AV-45 accumulated in cortical regions expected to be high in Abeta deposition (e.g., precuneus and frontal and temporal cortices) in AD patients; minimal accumulation of the tracer was seen in cortical regions of HCs. The cortical-to-cerebellar SUVRs in AD patients showed continual substantial increases through 30 min after administration, reaching a plateau within 50 min. The 10-min period from 50 to 60 min after administration was taken as a representative sample for further analysis. The cortical average SUVR for this period was 1.67 +/- 0.175 for patients with AD versus 1.25 +/- 0.177 for HCs. Spatially normalized DVRs generated from PET dynamic scans were highly correlated with SUVR (r = 0.58-0.88, P < 0.005) and were significantly greater for AD patients than for HCs in cortical regions but not in subcortical white matter or cerebellar regions. No clinically significant changes in vital signs, electrocardiogram, or laboratory values were observed.

CONCLUSION

(18)F-AV-45 was well tolerated, and PET showed significant discrimination between AD patients and HCs, using either a parametric reference region method (DVR) or a simplified SUVR calculated from 10 min of scanning 50-60 min after (18)F-AV-45 administration.

摘要

目的

评估（18）F 标记的 PET 淀粉样蛋白（Abeta）成像剂在评估老年认知障碍中的临床应用，为阿尔茨海默病（AD）病理学提供客观的测量方法。在此，我们介绍了一项（E）-4-（2-（6-（2-（2-（2-（18）F-氟乙氧基）乙氧基）乙氧基）吡啶-3-基）乙烯基）-N-甲基苯甲胺（（18）F-AV-45 或氟比他滨[已更正]F18）的临床试验结果。

方法

对 16 名 AD 患者（简易精神状态检查量表评分，19.3±3.1；平均年龄±标准差，75.8±9.2 岁）和 16 名认知正常对照者（简易精神状态检查量表评分，29.8±0.45；平均年龄±标准差，72.5±11.6 岁）进行了开放标签、多中心脑成像、代谢和安全性研究。在注射示踪剂后约 90 分钟内进行动态 PET 扫描（370MBq[10mCi]）。计算标准化摄取值和皮质小脑标准化摄取值比值（SUVRs）。在部分患者中使用简化参考组织方法生成分布容积比（DVR）参数图。

结果

11 名 AD 患者和 15 名 HC 患者有有效的 PET 数据。（18）F-AV-45 在 AD 患者的 Abeta 沉积高的皮质区域（如楔前叶和额颞叶皮质）积聚；HC 的皮质区域摄取示踪剂很少。AD 患者的皮质小脑 SUVR 在给药后 30 分钟内持续显著增加，50 分钟内达到平台期。给药后 50-60 分钟的 10 分钟时间段被视为进一步分析的代表性样本。该时间段的皮质平均 SUVR 为 1.67±0.175，AD 患者为 1.25±0.177。从 PET 动态扫描生成的空间归一化 DVR 与 SUVR 高度相关（r=0.58-0.88，P<0.005），AD 患者的皮质 DVR 明显高于 HC，但在皮质下白质或小脑区域则没有。未观察到生命体征、心电图或实验室值的临床显著变化。