[(11)C]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 [(11)C]methylation of a corresponding desmethyl precursor (DAA1123) with [(11)C]CH(3)I in the presence of NaH, with a 72+/-16% (corrected for decay) incorporation yield of radioactivity. After HPLC purification, [(11)C]DAA1106 was obtained with > or =98% radiochemical purity and specific activity of 90-156 GBq/micromol at the end of synthesis. After iv injection of [(11)C]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 [(11)C]DAA1106 with unlabeled DAA1106 and PBR-selective PK11195 displayed a significant reduction of radioactivity, suggesting a high specific binding of [(11)C]DAA1106 to PBR. Although this tracer was rapidly metabolized in the plasma, only [(11)C]DAA1106 was detected in the brain tissues, suggesting the specific binding in the brain due to the tracer itself. These findings revealed that [(11)C]DAA1106 is a potential and selective positron emitting radioligand for PBR.
Zhang
Ming-Rong
MR
Department of Medical Imaging, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, 263-8555 Chiba, Japan. zhang@nirs.go.jp
Kida
Takayo
T
Noguchi
Junko
J
Furutsuka
Kenji
K
Maeda
Jun
J
Suhara
Tetsuya
T
Suzuki
Kazutoshi
K
D000081:Acetamides / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D007553:Isotope Labeling / Q000379:methods; D008657:Metabolic Clearance Rate; D051379:Mice; D008815:Mice, Inbred Strains; D009928:Organ Specificity; D010647:Phenyl Ethers / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011963:Receptors, GABA-A / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
D000081:Acetamides; D002250:Carbon Radioisotopes; C118942:DAA 1106; D010647:Phenyl Ethers; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A