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

Abstract

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 [ 11C]methylation of a corresponding desmethyl precursor (DAA1123) with [ 11C]CH 3I in the presence of NaH, with a 72±16% (corrected for decay) incorporation yield of radioactivity. After HPLC purification, [ 11C]DAA1106 was obtained with ≥98% radiochemical purity and specific activity of 90–156 GBq/μmol at the end of synthesis. After iv injection of [ 11C]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 [ 11C]DAA1106 with unlabeled DAA1106 and PBR-selective PK11195 displayed a significant reduction of radioactivity, suggesting a high specific binding of [ 11C]DAA1106 to PBR. Although this tracer was rapidly metabolized in the plasma, only [ 11C]DAA1106 was detected in the brain tissues, suggesting the specific binding in the brain due to the tracer itself. These findings revealed that [ 11C]DAA1106 is a potential and selective positron emitting radioligand for PBR.