Quantitative Analysis of Amyloid Deposition in Alzheimer Disease Using PET and the Radiotracer 11C-AZD2184

Journal of Nuclear Medicine

Yoko Ikoma¹  Tetsuya Suhara¹  Makoto Higuchi¹  Hitoshi Shimada¹  Yoko Eguchi¹  Toshimitsu Fukumura¹  Yasuyuki Kimura¹  Takeshi Sasaki¹  Hitoshi Shinotoh¹  Kazunori Kawamura¹  Tomohisa Nagashima¹  Hironobu Fujiwara¹  Harumasa Takano¹  Keisuke Takahata¹  Hiroshi Ito¹  Shigeki Hirano¹  Tsuyoshi Nogami¹  Masayuki Suzuki¹  Chie Seki¹  Fumitoshi Kodaka¹  Éva Lindström Böö¹  Lars Farde¹ 

关键词: amyloid;    Alzheimer;    PET;    AZD2184;   

DOI  :  10.2967/jnumed.113.133793

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Characteristic neuropathologic changes in Alzheimer disease (AD) are amyloid-β deposits and neurofibrillary tangles. Recently, a new radioligand for amyloid senile plaques, 11C-labeled 5-(6-{[tert-butyl(dimethyl)silyl]oxy}-1,3-benzothiazol-2-yl)pyridin-2-amine (11C-AZD2184), was developed, and it was reported to show rapid brain uptake followed by rapid washout. In this study, 11C-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. Methods: After intravenous bolus injection of 11C-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. Results: 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. Conclusion: Although the white matter binding of 11C-AZD2184 may have some effect on cortical measurement, it can be concluded that the kinetic behavior of 11C-AZD2184 is suitable for quantitative analysis. The standardized uptake value ratio can be used as a validated measure of 11C-AZD2184 binding in clinical examinations without arterial input function.

【 授权许可】

Unknown