Quantitative Analysis of Peripheral Benzodiazepine Receptor in the Human Brain Using PET with 11C-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, C-11-AC-N-benzyl-N-ethyl-2-(7-methyl-8-oxo-2-pheyl-7,8-dihydro-9H-purin-9-yl)acetamide (C-11-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 C-11-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 C-11-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 (V-T) 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). V-T 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 K-1/k(2). 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 C-11-AC-5216 was in good agreement with previous PET studies of PBRs in the human brain. BPND is more appropriate for estimating C-11-AC-5216 binding than is VT because of the interindividual variation of K-1/k(2). C-11-AC-5216 is a promising PET ligand for quantifying PBR in the human brain.