Phase 1 Study of the Pittsburgh Compound B Derivative 18F-Flutemetamol in Healthy Volunteers and Patients with Probable Alzheimer Disease
Phase 1 Study of the Pittsburgh Compound B Derivative 18F-Flutemetamol in Healthy Volunteers and Patients with Probable Alzheimer Disease
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DOI：
10.2967/jnumed.109.063305
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发表时间：
2009-08-01
影响因子：
9.3
通讯作者：
Vandenberghe, Rik
中科院分区：
文献类型：
--
作者：
Nelissen, Natalie;Van Laere, Koen;Vandenberghe, Rik
C-11-匹兹堡化合物B（PiB）标志着A β淀粉样变性，A β淀粉样变性是阿尔茨海默病（AD）的关键发病过程。C-11-PiB的使用仅限于具有回旋加速器的中心。开发F-18标记的PiB的硫磺素衍生物，F-18-flutemetaline，可以大大提高这项新技术的可用性。该第1阶段研究的目的是进行F-18-flutemetaline的脑动力学建模，优化图像采集程序，并比较分析方法（步骤1），并在概念验证研究中比较AD患者与健康对照的F-18-flutemetaline脑保留（步骤1和2）。研究方法：在步骤1中，3名AD患者（简易精神状态检查，22-24）和3名老年健康对照者在注射约180 MBq的F-18-flutemetalone后0-90、150-180和220-250 min的窗口期间进行动态扫描，并进行动脉取样。我们比较了不同的分析方法（房室模型，Logan图形分析和标准化摄取值比），并确定了第2步的最佳采集窗口。第二步，5例AD患者（简易精神状态检查，20-26岁）和5名老年健康对照者在注射后80 - 170 min进行扫描。为了确定总体疗效，将步骤1和2合并，并使用小脑皮质作为参考区域计算标准化摄取值比值。结果：未报告不良事件。不同分析方法获得的摄取值之间存在很强的相关性。从注射后80分钟开始，新皮层与小脑摄取的比率最大，仅受扫描开始时间或持续时间的轻微影响。与健康对照组相比，AD患者的新皮质联合区和纹状体的标准化摄取值比值显著增加，而白色物质、小脑和脑桥的摄取在组间无差异。2例AD患者为F-18-氟美他莫阴性，1例健康对照为F-18-氟美他莫阳性。结论：可以容易地定量F-18-氟美托洛尔摄取。这项1期研究保证了进一步的研究，以验证这种F-18标记的PiB衍生物作为A β淀粉样变性的生物标志物。
C-11-Pittsburgh compound B (PiB) marks A beta amyloidosis, a key pathogenetic process in Alzheimer disease (AD). The use of C-11-PiB is limited to centers with a cyclotron. Development of the F-18-labeled thioflavin derivative of PiB, F-18-flutemetamol, could hugely increase the availability of this new technology. The aims of this phase 1 study were to perform brain kinetic modeling of F-18-flutemetamol, optimize the image acquisition procedure, and compare methods of analysis (step 1) and to compare F-18-flutemetamol brain retention in AD patients versus healthy controls in a proof-of-concept study (steps 1 and 2). Methods: In step 1, 3 AD patients (Mini-Mental State Examination, 22-24) and 3 elderly healthy controls were scanned dynamically during windows of 0-90, 150-180, and 220-250 min after injection of approximately 180 MBq of F-18-flutemetamol, with arterial sampling. We compared different analysis methods (compartmental modeling, Logan graphical analysis, and standardized uptake value ratios) and determined the optimal acquisition window for step 2. In step 2, 5 AD patients (Mini-Mental State Examination, 20-26) and 5 elderly healthy controls were scanned from 80 to 170 min after injection. To determine overall efficacy, steps 1 and 2 were pooled and standardized uptake value ratios were calculated using cerebellar cortex as a reference region. Results: No adverse events were reported. There was a strong correlation between uptake values obtained with the different analysis methods. From 80 min after injection onward, the ratio of neocortical to cerebellar uptake was maximal and only marginally affected by scan start time or duration. AD patients showed significantly increased standardized uptake value ratios in neocortical association zones and striatum, compared with healthy controls, whereas uptake in white matter, cerebellum, and pons did not differ between groups. Two AD patients were F-18-flutemetamol-negative and 1 healthy control was F-18-flutemetamol-positive. Conclusion: F-18-flutemetamol uptake can be readily quantified. This phase 1 study warrants further studies to validate this F-18-labeled derivative of PiB as a biomarker for A beta amyloidosis.