title: N-(5-Fluoro-2-phenoxyphenyl)-N-(2-[(131)I]iodo-5-me thoxybenzyl)acetamide: a potent iodinated radioligand for the peripheral-type benzodiazepine receptor in brain.
abstract: To image the peripheral-type benzodiazepine receptor (PBR) in vivo, we previously developed two positron emission tomography (PET) ligands, N-(2-[11C],5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide ([11C]1a) and its [18F]fluoroethyl analogue ([18F]1b), for the investigation of PBR in the living human brain. This time, using 1a as a leading compound, we designed two novel iodinated analogues, N-(5-fluoro-2-phenoxyphenyl)-N-(2-iodo-5-methoxybenzyl)acetamide (3a) and N-(2,5-dimethoxybenzyl)-N-(5-iodo-2-phenoxyphenyl)acetamide (3b) for the PBR imaging. Ligands 3 were synthesized by the iodination of tributystannyl precursors 10. Radiolabeling for 3 with 131I was carried out by the reaction of 10 with [131I]NaI using H2O2 as an oxidizing agent. In vitro competition experiments determined that 3a exhibited both high affinity and selectivity for PBR (IC50: 7.8 nM) vs CBR (>1 microM). Biodistribution study in mice determined that [131I]3a had a high radioactivity level (1.69% dose/g) in the brain, and its distribution pattern in the brain was consistent with the known distribution of PBR in rodents. Ex vivo autoradiography of the rat brain gave visual evidence that [131I]3a was a potent and specific radioligand for PBR.
authors.affiliation: Radiochemistry Section, Department of Molecular Probe, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. zhang@nirs.go.jp
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kumata
authors.forename: Jun
authors.initials: J
authors.lastname: Maeda
authors.forename: Terushi
authors.initials: T
authors.lastname: Haradahira
authors.forename: Junko
authors.initials: J
authors.lastname: Noguchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008024:Ligands; D008297:Male; D051379:Mice; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D000081:Acetamides; D000814:Aniline Compounds; D007457:Iodine Radioisotopes; D008024:Ligands; C518311:N-(5-fluoro-2-phenoxyphenyl)-N-(2-iodo-5-methoxybenzyl)acetamide; D011963:Receptors, GABA-A