title: Evaluation of N-benzyl-N-[11C]methyl-2- (7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([11C]DAC) as a novel translocator protein (18 kDa) radioligand in kainic acid-lesioned rat.
abstract: The aim of this study was to evaluate N-benzyl-N-[11C]methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([11C]DAC) as a new translocator protein (18 kDa) [TSPO, formerly known as the peripheral-type benzodiazepine receptor (PBR)] positron emission tomography (PET) ligand in normal mice and unilateral kainic acid (KA)-lesioned rats. DAC is a derivative of AC-5216, which is a potent and selective PET ligand for the clinical investigation of TSPO. The binding affinity and selectivity of DAC for TSPO were similar to those of AC-5216, and DAC was less lipophilic than AC-5216. The distribution pattern of [11C]DAC was in agreement with TSPO distribution in rodents. No radioactive metabolite of [11C]DAC was found in the mouse brain, although it was metabolized rapidly in mouse plasma. Using small-animal PET, we examined the in vivo binding of [11C]DAC for TSPO in KA-lesioned rats. [11C]DAC and [11C]AC-5216 exhibited similar brain uptake in the lesioned and nonlesioned striatum, respectively. The binding of [11C]DAC to TSPO was increased significantly in the lesioned striatum, and [(11)C]DAC showed good contrast between the lesioned and nonlesioned striatum (the maximum ratio was about threefold). In displacement experiments, the uptake of [11C]DAC in the lesioned striatum was eventually blocked using an excess of either unlabeled DAC or PK11195 injected. [11C]DAC had high in vivo specific binding to TSPO in the injured rat brain. Therefore, [11C]DAC is a useful PET ligand for TSPO imaging, and its specific binding to TSPO is suitable as a new biomarker for brain injury.
authors: Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, Japan.
authors: Kazuhiko
authors: K
authors: Yanamoto
authors: Tomoteru
authors: T
authors: Yamasaki
authors: Katsushi
authors: K
authors: Kumata
authors: Joji
authors: J
authors: Yui
authors: Chika
authors: C
authors: Odawara
authors: Kazunori
authors: K
authors: Kawamura
authors: Akiko
authors: A
authors: Hatori
authors: Osamu
authors: O
authors: Inoue
authors: Masatoshi
authors: M
authors: Yamaguchi
authors: Kazutoshi
authors: K
authors: Suzuki
authors: Ming-Rong
authors: MR
authors: Zhang
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007608:Kainic Acid / Q000633:toxicity; D008024:Ligands; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography; D011687:Purines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000737:chemistry / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D018690:Excitatory Amino Acid Agonists; D008024:Ligands; C502525:N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide; D011687:Purines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human; D007608:Kainic Acid