Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and
Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; and.
J Nucl Med. 2014 Jun;55(6):932-8. doi: 10.2967/jnumed.113.133793. Epub 2014 Apr 14.
Characteristic neuropathologic changes in Alzheimer disease (AD) are amyloid-β deposits and neurofibrillary tangles. Recently, a new radioligand for amyloid senile plaques, (11)C-labeled 5-(6-{[tert-butyl(dimethyl)silyl]oxy}-1,3-benzothiazol-2-yl)pyridin-2-amine ((11)C-AZD2184), was developed, and it was reported to show rapid brain uptake followed by rapid washout. In this study, (11)C-AZD2184 binding in control subjects and AD patients was examined in more detail by compartment model analysis using a metabolite-corrected arterial input function. The accuracy of simplified quantitative methods using a reference brain region was also evaluated.
After intravenous bolus injection of (11)C-AZD2184, a dynamic PET scan was obtained for 90 min in 6 control subjects and 8 AD patients. To obtain the arterial input function, arterial blood sampling and high-performance liquid chromatography analysis were performed.
Time-activity curves in all brain regions could be described using the standard 2-tissue-compartment model. The total distribution volume ratios to reference region (DVR) in cerebral cortical regions were significantly higher in AD patients than in control subjects. Although there was no conspicuous accumulation of radioactivity in white matter as compared with other amyloid radioligands, DVR values in the centrum semiovale were more than 1 for both control subjects and AD patients, suggesting binding to myelin. The standardized uptake value ratio calculated from integrated time-activity curves in brain regions and the reference region was statistically in good agreement with DVR.
Although the white matter binding of (11)C-AZD2184 may have some effect on cortical measurement, it can be concluded that the kinetic behavior of (11)C-AZD2184 is suitable for quantitative analysis. The standardized uptake value ratio can be used as a validated measure of (11)C-AZD2184 binding in clinical examinations without arterial input function.
阿尔茨海默病（AD）的特征性神经病理学改变为β淀粉样蛋白沉积和神经纤维缠结。最近，一种新的用于淀粉样蛋白斑块的放射性配体，（11）C 标记的 5-（6-{[叔丁基（二甲基）硅基]氧基}-1,3-苯并噻唑-2-基）吡啶-2-胺（（11）C-AZD2184）被开发出来，据报道其具有快速的脑摄取，随后快速清除。在这项研究中，通过使用校正代谢物的动脉输入函数的房室模型分析，更详细地检查了（11）C-AZD2184 在对照受试者和 AD 患者中的结合情况。还评估了使用参考脑区的简化定量方法的准确性。
静脉注射（11）C-AZD2184 后，6 名对照受试者和 8 名 AD 患者进行了 90 分钟的动态 PET 扫描。为了获得动脉输入函数，进行了动脉采血和高效液相色谱分析。
所有脑区的时间-活性曲线都可以使用标准的 2 组织房室模型来描述。大脑皮质区域的总分布容积比（DVR）在 AD 患者中明显高于对照组。虽然与其他淀粉样蛋白配体相比，放射性配体在白质中的积累并不明显，但半卵圆中心的 DVR 值均大于 1，提示与髓鞘结合。从脑区和参考区整合时间-活性曲线计算的标准化摄取值比与 DVR 具有统计学上的良好一致性。
尽管（11）C-AZD2184 与白质的结合可能对白质测量有一定影响，但可以得出结论，（11）C-AZD2184 的动力学行为适合定量分析。在没有动脉输入函数的情况下，标准化摄取值比可作为（11）C-AZD2184 结合的验证指标用于临床检查。
