Quantitative analysis of peripheral benzodiazepine receptor in the human brain using PET with (11)C-AC-5216

Miyoshi M, Ito H, Arakawa R, Takahashi H, Takano H, Higuchi M, Okumura M, Otsuka T, Kodaka F, Sekine M, Sasaki T, Fujie S, Seki C, Maeda J, Nakao R, Zhang MR, Fukumura T, Matsumoto M, Suhara T

J. Nucl. Med. 2009 Jul;50(7):1095-101

PMID: 19525461


UNLABELLED: 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).

CONCLUSION: 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.