Quantitative Analysis of Peripheral Benzodiazepine Receptor in the Human Brain Using PET with 11C-AC-5216

Journal of Nuclear Medicine

Tatsui Otsuka¹  Hidehiko Takahashi¹  Michie Miyoshi¹  Tetsuya Suhara¹  Makoto Higuchi¹  Mizuho Sekine¹  Ryosuke Arakawa¹  Saori Fujie¹  Toshimitsu Fukumura¹  Ryuji Nakao¹  Takeshi Sasaki¹  Masaki Okumura¹  Harumasa Takano¹  Hiroshi Ito¹  Jun Maeda¹  Masayasu Matsumoto¹  Chie Seki¹  Fumitoshi Kodaka¹  Ming-Rong Zhang¹ 

关键词: ¹¹C-AC-5216;    peripheral benzodiazepine receptor;    microglia;    human brain;    positron emission tomography;   

DOI  :  10.2967/jnumed.109.062554

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Peripheral benzodiazepine receptor (PBR) is upregulated in activated glial cells and is therefore a useful biomarker for inflammation in the brain and neurodegenerative disorders. We developed a new PET radioligand, 11C-AC-N-benzyl-N-ethyl-2-(7-methyl-8-oxo-2-pheyl-7,8-dihydro-9H-purin-9-yl)acetamide (11C-AC-5216), that allows the imaging and quantification of PBRs in monkey and mouse brains. The aim of this study was to evaluate a quantification method of 11C-AC-5216 binding in the human brain. Methods: A 90-min dynamic PET scan was obtained for each of 12 healthy men after an intravenous injection of 11C-AC-5216. Regions of interest were drawn on several brain regions. Binding potential, compared with nondisplaceable uptake (BPND), was calculated by a nonlinear least-squares fitting (NLS) method with the 2-tissue-compartment model, and total volume of distribution (VT) was estimated by NLS and graphical analysis methods. Results: BPND was highest in the thalamus (4.6 ± 1.0) and lowest in the striatum (3.5 ± 0.7). VT obtained by NLS or graphical analysis showed regional distribution similar to BPND. However, there was no correlation between BPND and VT because of the interindividual variation of K1/k2. BPND obtained with data from a scan time of 60 min was in good agreement with that from a scan time of 90 min (r = 0.87). Conclusion: Regional distribution of 11C-AC-5216 was in good agreement with previous PET studies of PBRs in the human brain. BPND is more appropriate for estimating 11C-AC-5216 binding than is VT because of the interindividual variation of K1/k2. 11C-AC-5216 is a promising PET ligand for quantifying PBR in the human brain.

【 授权许可】

Unknown