Nelissen Natalie, Van Laere Koen, Thurfjell Lennart, Owenius Rikard, Vandenbulcke Mathieu, Koole Michel, Bormans Guy, Brooks David J, Vandenberghe Rik
Laboratory for Cognitive Neurology, K.U. Leuven, Leuven, Belgium.
J Nucl Med. 2009 Aug;50(8):1251-9. doi: 10.2967/jnumed.109.063305. Epub 2009 Jul 17.
(11)C-Pittsburgh compound B (PiB) marks Abeta amyloidosis, a key pathogenetic process in Alzheimer disease (AD). The use of (11)C-PiB is limited to centers with a cyclotron. Development of the (18)F-labeled thioflavin derivative of PiB, (18)F-flutemetamol, could hugely increase the availability of this new technology. The aims of this phase 1 study were to perform brain kinetic modeling of (18)F-flutemetamol, optimize the image acquisition procedure, and compare methods of analysis (step 1) and to compare (18)F-flutemetamol brain retention in AD patients versus healthy controls in a proof-of-concept study (steps 1 and 2).
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 (18)F-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.
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 (18)F-flutemetamol-negative and 1 healthy control was (18)F-flutemetamol-positive.
(18)F-flutemetamol uptake can be readily quantified. This phase 1 study warrants further studies to validate this (18)F-labeled derivative of PiB as a biomarker for Abeta amyloidosis.
（11）C-匹兹堡化合物B（PiB）可标记β淀粉样变性，这是阿尔茨海默病（AD）的关键致病过程。（11）C-PiB的使用仅限于拥有回旋加速器的中心。PiB的（18）F标记硫黄素衍生物（18）F-氟代甲磺酸的开发可能会大大提高这项新技术的可用性。这项1期研究的目的是对（18）F-氟代甲磺酸进行脑动力学建模，优化图像采集程序，并比较分析方法（步骤1），以及在一项概念验证研究中比较AD患者与健康对照者的（18）F-氟代甲磺酸脑摄取情况（步骤1和2）。
在步骤1中，3例AD患者（简易精神状态检查表评分，22 - 24）和3例老年健康对照者在注射约180 MBq的（18）F-氟代甲磺酸后的0 - 90、150 - 180和220 - 250分钟窗口内进行动态扫描，并采集动脉血样。我们比较了不同的分析方法（房室模型、洛根图形分析和标准化摄取值比率），并确定了步骤2的最佳采集窗口。在步骤2中，5例AD患者（简易精神状态检查表评分，20 - 26）和5例老年健康对照者在注射后80至170分钟进行扫描。为了确定总体疗效，将步骤1和2合并，并以小脑皮质作为参考区域计算标准化摄取值比率。
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。注射后80分钟起，新皮质与小脑摄取的比率最大，且受扫描开始时间或持续时间的影响很小。与健康对照者相比，AD患者新皮质联合区和纹状体的标准化摄取值比率显著增加，而白质、小脑和脑桥的摄取在两组之间没有差异。2例AD患者为（18）F-氟代甲磺酸阴性，1例健康对照者为（18）F-氟代甲磺酸阳性。
（18）F-氟代甲磺酸的摄取可以很容易地进行定量。这项1期研究值得进一步研究，以验证这种PiB的（18）F标记衍生物作为β淀粉样变性生物标志物的有效性。
