Novel peripheral benzodiazepine receptor ligand [11C]DAA1106 for PET:: An imaging tool for glial cells in the brain

Peripheral benzodiazepine receptor (PBR) is expressed in most organs and its expression is reported to be increased in activated microglia in the brain. [C-11] PK11195 has been widely used for the in vivo imaging of PBRs, but its signal in the brain was not high enough for stable quantitative analysis. We synthesized a novel positron emission tomography (PET) ligand, [C-11]DAA1106, for PBR and investigated its in vivo properties in rat and monkey brain. High uptake of [C-11]DAA1106 was observed in the olfactory bulb and choroid plexus area, followed by the pons/medulla and cerebellum by in vivo autoradiography of rat brain, correlating with the binding in vitro. [C-11]DAA1106 binding was increased in the dorsal hippocampus with neural destruction, suggesting glial reaction. [C-11]DAA1106 binding was both inhibited and displaced by 1.0 mg/kg of DAA1106 and 5 mg/kg of PK11195 by 80% and 70%, respectively. Specific binding was estimated as 80% of total binding. [C-11]DAA1106 binding was four times higher compared to the binding of [C-11]PK11195 in the monkey occipital cortex. These results indicated that [C-11]DAA1106 might be a good ligand for in vivo imaging of PBR. Synapse 52:283-291, 2004. (C) 2004 Wiley-Liss, Inc.