[11C]DAA1106:: Radiosynthesis and in vivo binding to peripheral benzodiazepine receptors in mouse brain

DAA1106 (N-(2,5-Dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide), is a potent and selective ligand for peripheral benzodiazepine receptors (PBR) in mitochondrial fractions of rat (K-i=0.043 nM) and monkey (K-i=0.188 nM) brains. This compound was labeled by [C-11]methylation of a corresponding desmethyl precursor (DAA1123) with [C-11]CH3I in the presence of NaH, with a 72+/-16% (corrected for decay) incorporation yield of radioactivity. After HPLC purification, [C-11]DAA1106 was obtained with 98% radiochemical purity and specific activity of 90-156 GBq/mumol at the end of synthesis. After iv injection of [C-11]DAA1106 into mice, high accumulations of radioactivity were found in the olfactory bulb and cerebellum, the high PBR density regions in the brain. Coinjection of [C-11]DAA1106 with unlabeled DAA1106 and PBR-selective PK11195 displayed a significant reduction of radioactivity, suggesting a high specific binding of [C-11]DAA1106 to PBR. Although this tracer was rapidly metabolized in the plasma, only [C-11]DAA1106 was detected in the brain tissues, suggesting the specific binding in the brain due to the tracer itself. These findings revealed that [C-11]DAA1106 is a potential and selective positron emitting radioligand for PBR. (C) 2003 Elsevier Inc. All rights reserved.