Clinical Validation of 18F-AZD4694, an Amyloid-β-Specific PET Radioligand
Clinical Validation of 18F-AZD4694, an Amyloid-β-Specific PET Radioligand
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DOI：
10.2967/jnumed.111.094029
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发表时间：
2012-03-01
影响因子：
9.3
通讯作者：
Farde, Lars
中科院分区：
文献类型：
--
作者：
Cselenyi, Zsolt;Jonhagen, Maria Eriksdotter;Farde, Lars
随着C-11-匹兹堡化合物B的发明，使用PET的淀粉样蛋白-β成像促进了阿尔茨海默病（AD）的研究。这种成像方法有希望用于诊断目的和评估疾病修饰疗法。广泛的临床应用需要具有高特异性和低非特异性结合的F-18标记的淀粉样蛋白-β放射性配体。本PET研究的目的是检查人类受试者中的放射性配体F-18-AZD 4694。方法：6名对照受试者和10名临床诊断的AD患者接受F-18-AZD 4694 PET检查和结构MRI扫描。其中，4名对照和4名患者进行了第二次PET检查，用于重新测试分析。进行动脉采样以推导用于传统隔室建模的代谢物校正的血浆输入函数。此外，还采用了几种简化的定量方法，包括参考Logan方法和简单比率方法。结果：静脉注射F-18-AZD 4694后，脑内迅速出现放射性。在患者中，预期含有淀粉样蛋白b的区域放射性高，而在对照组中，放射性低且均匀分布。小脑（参考区域）中的结合率较低，且组间相似。特异性结合是可逆的，在高放射性区域注射后约27 min达到峰值。时间-活性曲线可用二组织房室模型描述。使用房室模型和简化方法获得的分布体积比估计值高度相关。在灰质中，对照受试者晚期计算的标准化摄取值比值和使用参考Logan方法估计的分布容积比值（分别为1.08 [11%]和1.01 [6%]）显著低于AD患者（分别为2.15 [24%]和1.62 [18%]）。在非侵入性方法中，使用参考Logan发现了最低的重测变异性，在大脑区域之间变化在4%和6%之间。结论：非侵入性定量方法提供了有效的估计淀粉样蛋白b结合。由于使用放射性同位素（F-18）标记，放射性配体具有广泛的临床应用潜力。F-18-AZD 4694满足了有前景的淀粉样β放射性配体的要求，可用于诊断和评估AD的疾病修饰疗法。
Pioneered with the invention of C-11-Pittsburgh compound B, amyloid-beta imaging using PET has facilitated research in Alzheimer disease (AD). This imaging approach has promise for diagnostic purposes and evaluation of disease-modifying therapies. Broad clinical use requires an F-18-labeled amyloid-beta radioligand with high specific and low nonspecific binding. The aim of the present PET study was to examine the radioligand F-18-AZD4694 in human subjects. Methods: Six control subjects and 10 clinically diagnosed AD patients underwent PET examination with F-18-AZD4694 and a structural MRI scan. Of these, 4 controls and 4 patients underwent a second PET examination for test-retest analysis. Arterial sampling was done to derive a metabolite-corrected plasma input function for traditional compartment modeling. Besides, several simplified quantitative approaches were applied, including the reference Logan approach and simple ratio methods. Results: After intravenous injection of F-18-AZD4694, radioactivity appeared rapidly in brain. In patients, radioactivity was high in regions expected to contain amyloid-b, whereas in controls, radioactivity was low and homogenously distributed. Binding in cerebellum, a reference region, was low and similar between the groups. Specific binding was reversible and peaked at about 27 min after injection in regions with high radioactivity. The time-activity curves could be described using the 2-tissue-compartment model. Distribution volume ratio estimates obtained using compartment models and simplified methods were highly correlated. Standardized uptake value ratios calculated at late times and distribution volume ratios estimated with the reference Logan approach were, in gray matter, significantly lower in control subjects (1.08 [11%] and 1.01 [6%], respectively) than in AD patients (2.15 [24%] and 1.62 [18%], respectively). Among non-invasive methods, the lowest test-retest variability was found with reference Logan, varying between 4% and 6% across brain regions. Conclusion: Noninvasive quantitative approaches provide valid estimates of amyloid-b binding. Because of the radioisotope (F-18) used for labeling, the radioligand has potential for wide clinical application. F-18-AZD4694 satisfies the requirements for a promising amyloid-beta radioligand both for diagnostic use and for evaluation of disease-modifying therapies in AD.