title: [11C]-MeJDTic: a novel radioligand for kappa-opioid receptor positron emission tomography imaging.
abstract: BACKGROUND
  Radiopharmaceuticals that can bind selectively the kappa-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of kappa-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the kappa-opioid receptor in mice.
  
  
  METHODS
  [(11)C]-MeJDTic was prepared by methylation of JDTic with [(11)C]-methyl triflate. The binding of [(11)C]-MeJDTic to kappa-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice.
  
  
  RESULTS
  [(11)C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the kappa receptor is largely expressed. [(11)C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a kappa referring agonist), morphine (a mu agonist) and naltrindole (a delta antagonist) demonstrated that this uptake was the result of specific binding to the kappa-opioid receptor.
  
  
  CONCLUSIONS
  These findings suggested that [(11)C]-MeJDTic appeared to be a promising selective "lead" radioligand for kappa-opioid receptor PET imaging.
authors.affiliation: Groupe de Développements Méthodologiques en Tomographie par Emission de Positons, DSV/DRM UMR Commissariat à l'Energie Atomique, 2E, Université de Caen-Basse Normandie, Centre Cyceron, Caen Cedex, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Poisnel
authors.forename: Farhana
authors.initials: F
authors.lastname: Oueslati
authors.forename: Martine
authors.initials: M
authors.lastname: Dhilly
authors.forename: Jérôme
authors.initials: J
authors.lastname: Delamare
authors.forename: Cécile
authors.initials: C
authors.lastname: Perrio
authors.forename: Danièle
authors.initials: D
authors.lastname: Debruyne
authors.forename: Louisa
authors.initials: L
authors.lastname: Barré
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003627:Data Interpretation, Statistical; D007202:Indicators and Reagents; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008745:Methylation; D051379:Mice; D010880:Piperidines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C531564:7-hydroxy-N-(1-((4-(3-hydroxyphenyl)-3,4-dimethyl-1--piperidinyl)methyl)-2-methylpropyl)-1,2,3,4-tetrahydro-2-methylisoquinolinecarboxamide; C433814:7-hydroxy-N-(1-((4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl)methyl)-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide; D007202:Indicators and Reagents; D010880:Piperidines; D019275:Radiopharmaceuticals; D017473:Receptors, Opioid, kappa; D044005:Tetrahydroisoquinolines