title: Radiosynthesis and quality control of [11C]TASP457 as a clinically useful PET ligand for imaging of histamine H3receptors in human brain.
abstract: BACKGROUND
  Recently, 6-[(1-cyclobutylpiperidin-4-yl)oxy]-1-(6-[11C]methoxypyridin-3-yl)-3,4-dihydroquinolin-2(1H)-one ([11C]TASP457, [11C]2) has been developed as a novel PET ligand for histamine H3receptors in brain. [11C]2 is potentially suitable for imaging H3receptors in rat and monkey brains, which has motivated us to perform first-in-human study of [11C]2 for qualifying H3receptors in human brain. In this paper, we report an efficient radiosynthesis of [11C]2 to obtain sufficient radioactivity and high quality for clinical application.
  
  
  METHODS
  In manual synthesis, we optimized the reaction conditions of desmethyl precursor 1, which contains a 2-hydroxypyridine moiety, with [11C]MeI or [11C]MeOTf. After optimization, we performed automated synthesis and quality control of [11C]2.
  
  
  RESULTS
  Bubbling [11C]MeOTf into a heated mixture of precursor 1 and cesium carbonate in DMF at 100°C for 90s produced [11C]2 with decay-corrected radiochemical yields of (based on [11C]CO2) 7.9±1.8% (n=78). The specific activity of [11C]2 was 156±52GBq/μmol (n=78) at the end of synthesis. The total synthesis time was approximately 35min from the end of bombardment. All the quality control results of [11C]2 were in compliance with our in-house quality control/assurance specifications.
  
  
  CONCLUSIONS
  We radiosynthesized [11C]TASP457 ([11C]2) with sufficient amounts of radioactivity and high quality for clinical usefulness. This radioligand is being used for PET assessment of H3receptors in human brain in our facility.
authors: Department of Radiopharmaceuticals Development, National Institute of Radiological Science, Chiba 263-8555, Japan.
authors: Masayuki
authors: M
authors: Hanyu
authors: Department of Radiopharmaceuticals Development, National Institute of Radiological Science, Chiba 263-8555, Japan.
authors: Kazunori
authors: K
authors: Kawamura
authors: Department of Radiopharmaceuticals Development, National Institute of Radiological Science, Chiba 263-8555, Japan.
authors: Makoto
authors: M
authors: Takei
authors: Department of Radiopharmaceuticals Development, National Institute of Radiological Science, Chiba 263-8555, Japan; SHI Accelerator Service Ltd., Tokyo 141-0032, Japan.
authors: Kenji
authors: K
authors: Furutsuka
authors: Department of Radiopharmaceuticals Development, National Institute of Radiological Science, Chiba 263-8555, Japan; Tokyo Nuclear Services Ltd., Tokyo 110-0016, Japan.
authors: Satoshi
authors: S
authors: Shiomi
authors: Department of Radiopharmaceuticals Development, National Institute of Radiological Science, Chiba 263-8555, Japan; Tokyo Nuclear Services Ltd., Tokyo 110-0016, Japan.
authors: Tomoya
authors: T
authors: Fujishiro
authors: Department of Radiopharmaceuticals Development, National Institute of Radiological Science, Chiba 263-8555, Japan; SHI Accelerator Service Ltd., Tokyo 141-0032, Japan.
authors: Masanao
authors: M
authors: Ogawa
authors: Department of Radiopharmaceuticals Development, National Institute of Radiological Science, Chiba 263-8555, Japan; SHI Accelerator Service Ltd., Tokyo 141-0032, Japan.
authors: Nobuki
authors: N
authors: Nengaki
authors: Department of Radiopharmaceuticals Development, National Institute of Radiological Science, Chiba 263-8555, Japan.
authors: Hiroki
authors: H
authors: Hashimoto
authors: Department of Radiopharmaceuticals Development, National Institute of Radiological Science, Chiba 263-8555, Japan.
authors: Toshimitsu
authors: T
authors: Fukumura
authors: Department of Radiopharmaceuticals Development, National Institute of Radiological Science, Chiba 263-8555, Japan. Electronic address: zhang.ming-rong@qst.go.jp.
authors: Ming-Rong
authors: MR
authors: Zhang
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D011786:Quality Control; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D011854:Radiochemistry / Q000379:methods* / Q000592:standards; D018100:Receptors, Histamine H3 / Q000378:metabolism*
chemical_list: D008024:Ligands; D011725:Pyridines; D015363:Quinolones; D018100:Receptors, Histamine H3; C000619211:TASP457
keywords: 2-Hydroxypyridine; Histamine H(3) receptor; PET; Quality control; [(11)C]TASP457