title: Radiosynthesis and in vivo evaluation of two imidazopyridineacetamides, [(11)C]CB184 and [ (11)C]CB190, as a PET tracer for 18 kDa translocator protein: direct comparison with [ (11)C](R)-PK11195.
abstract: OBJECTIVE
  We report synthesis of two carbon-11 labeled imidazopyridines TSPO ligands, [(11)C]CB184 and [(11)C]CB190, for PET imaging of inflammatory process along with neurodegeneration, ischemia or brain tumor. Biodistribution of these compounds was compared with that of [(11)C]CB148 and [(11)C](R)-PK11195.
  
  
  METHODS
  Both [(11)C]CB184 and [(11)C]CB190 having (11)C-methoxyl group on an aromatic ring were readily prepared using [(11)C]methyl triflate. Biodistribution and metabolism of the compounds were examined with normal mice. An animal PET study using 6-hydroxydopamine treated rats as a model of neurodegeneration was pursued for proper estimation of feasibility of the radioligands to determine neuroinflammation process.
  
  
  RESULTS
  [(11)C]CB184 and [(11)C]CB190 were obtained via O-methylation of corresponding desmethyl precursor using [(11)C]methyl triflate in radiochemical yield of 73 % (decay-corrected). In vivo validation as a TSPO radioligand was carried out using normal mice and lesioned rats. In mice, [(11)C]CB184 showed more uptake and specific binding than [(11)C]CB190. Metabolism studies showed that 36 % and 25 % of radioactivity in plasma remained unchanged 30 min after intravenous injection of [(11)C]CB184 and [(11)C]CB190, respectively. In the PET study using rats, lesioned side of the brain showed significantly higher uptake than contralateral side after i.v. injection of either [(11)C]CB184 or [(11)C](R)-PK11195. Indirect Logan plot analysis revealed distribution volume ratio (DVR) between the two sides which might indicate lesion-related elevation of TSPO binding. The DVR was 1.15 ± 0.10 for [(11)C](R)-PK11195 and was 1.15 ± 0.09 for [(11)C]CB184.
  
  
  CONCLUSIONS
  The sensitivity to detect neuroinflammation activity was similar for [(11)C]CB184 and [(11)C](R)-PK11195.
authors.affiliation: Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi, 474-8522, Japan, hatanok@md.tsukuba.ac.jp.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hatano
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Sekimata
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamada
authors.forename: Junichiro
authors.initials: J
authors.lastname: Abe
authors.forename: Kengo
authors.initials: K
authors.lastname: Ito
authors.forename: Mikako
authors.initials: M
authors.lastname: Ogawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Magata
authors.forename: Jun
authors.initials: J
authors.lastname: Toyohara
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
authors.forename: Giovanni
authors.initials: G
authors.lastname: Biggio
authors.forename: Mariangela
authors.initials: M
authors.lastname: Serra
authors.forename: Valentino
authors.initials: V
authors.lastname: Laquintana
authors.forename: Nunzio
authors.initials: N
authors.lastname: Denora
authors.forename: Andrea
authors.initials: A
authors.lastname: Latrofa
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Trapani
authors.forename: Gaetano
authors.initials: G
authors.lastname: Liso
authors.forename: Hiromi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Makoto
authors.initials: M
authors.lastname: Sawada
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nomura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Toyama
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D001597:Benzylidene Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000737:chemistry; D002352:Carrier Proteins / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008698:Mesylates / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D009019:Morphinans / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000442:Octanols / Q000737:chemistry; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D001597:Benzylidene Compounds; C463819:Bzrp protein, mouse; C096583:CB 182; C000604347:CB190 compound; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D007093:Imidazoles; D007546:Isoquinolines; D008698:Mesylates; D009019:Morphinans; D000442:Octanols; D011725:Pyridines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D014867:Water; C069997:Tspo protein, rat; C078465:methyl triflate; C037850:PK 11195