TY - JOUR
T1 - Quantitative analysis of peripheral benzodiazepine receptor in the human brain using PET with 11C-AC-5216
AU - Miyoshi, Michie
AU - Ito, Hiroshi
AU - Arakawa, Ryosuke
AU - Takahashi, Hidehiko
AU - Takano, Harumasa
AU - Higuchi, Makoto
AU - Okumura, Masaki
AU - Otsuka, Tatsui
AU - Kodaka, Fumitoshi
AU - Sekine, Mizuho
AU - Sasaki, Takeshi
AU - Fujie, Saori
AU - Seki, Chie
AU - Maeda, Jun
AU - Nakao, Ryuji
AU - Zhang, Ming Rong
AU - Fukumura, Toshimitsu
AU - Matsumoto, Masayasu
AU - Suhara, Tetsuya
PY - 2009/7/1
Y1 - 2009/7/1
N2 - 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 11CAC-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 K 1/k2. 11C-AC-5216 is a promising PET ligand for quantifying PBR in the human brain.
AB - 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 11CAC-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 K 1/k2. 11C-AC-5216 is a promising PET ligand for quantifying PBR in the human brain.
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U2 - 10.2967/jnumed.109.062554
DO - 10.2967/jnumed.109.062554
M3 - Article
C2 - 19525461
AN - SCOPUS:67650075027
SN - 0161-5505
VL - 50
SP - 1095
EP - 1101
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 7
ER -
