Quantitative analysis of peripheral benzodiazepine receptor in the human brain using PET with (11)C-AC-5216.
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, (11)C-AC-N-benzyl-N-ethyl-2-(7-methyl-8-oxo-2-pheyl-7,8-dihydro-9H-purin-9-yl)acetamide ((11)C-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 (11)C-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 (11)C-AC-5216. Regions of interest were drawn on several brain regions. Binding potential, compared with nondisplaceable uptake (BP(ND)), was calculated by a nonlinear least-squares fitting (NLS) method with the 2-tissue-compartment model, and total volume of distribution (V(T)) was estimated by NLS and graphical analysis methods.


RESULTS
BP(ND) was highest in the thalamus (4.6 +/- 1.0) and lowest in the striatum (3.5 +/- 0.7). V(T) obtained by NLS or graphical analysis showed regional distribution similar to BP(ND). However, there was no correlation between BP(ND) and V(T) because of the interindividual variation of K(1)/k(2). BP(ND) 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).


CONCLUSIONS
Regional distribution of (11)C-AC-5216 was in good agreement with previous PET studies of PBRs in the human brain. BP(ND) is more appropriate for estimating (11)C-AC-5216 binding than is V(T) because of the interindividual variation of K(1)/k(2). (11)C-AC-5216 is a promising PET ligand for quantifying PBR in the human brain.
Miyoshi
Michie
M
Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
Ito
Hiroshi
H
Arakawa
Ryosuke
R
Takahashi
Hidehiko
H
Takano
Harumasa
H
Higuchi
Makoto
M
Okumura
Masaki
M
Otsuka
Tatsui
T
Kodaka
Fumitoshi
F
Sekine
Mizuho
M
Sasaki
Takeshi
T
Fujie
Saori
S
Seki
Chie
C
Maeda
Jun
J
Nakao
Ryuji
R
Zhang
Ming-Rong
MR
Fukumura
Toshimitsu
T
Matsumoto
Masayasu
M
Suhara
Tetsuya
T
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003198:Computer Simulation; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate; D008959:Models, Neurological; D049268:Positron-Emission Tomography / Q000379:methods*; D011687:Purines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011963:Receptors, GABA-A / Q000378:metabolism*; D014018:Tissue Distribution; D055815:Young Adult
D002250:Carbon Radioisotopes; C502525:N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide; D011687:Purines; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A