title: Radiosynthesis and in vivo evaluation of [11C]-labelled pyrrole-2-carboxamide derivates as novel radioligands for PET imaging of monoamine oxidase A.
abstract: BACKGROUND
  Since MAO-A is an enzyme involved in the metabolism of neurotransmitters, fluctuations in MAO-A functionality are associated with psychiatric and neurological disorders as well as with tobacco addiction and behaviour. This study reports the radiolabelling of two [(11)C]-labelled pyrrole-2-carboxamide derivates, RS 2315 and RS 2360, along with the characterization of their in vivo properties.
  
  
  METHODS
  The radiolabelling of [(11)C]-RS 2315 and [(11)C]-RS 2360 was accomplished by alkylation of their amide precursors with [(11)C]CH(3)I. Biodistribution, blocking and metabolite studies of both tracers were performed in NMRI mice. Finally, a PET study in Sprague-Dawley rats was performed for [(11)C]-RS 2360.
  
  
  RESULTS
  Both tracers were obtained in a radiochemical yield of approximately 30% with radiochemical purity of >98%. Biodistribution studies showed high brain uptake followed by rapid brain clearance for both radiotracers. In the brain, [(11)C]-RS 2360 was more stable than [(11)C]-RS 2315. Blocking studies in mice could not demonstrate specificity of [(11)C]-RS 2315 towards MAO-A or MAO-B. The blocking and imaging study with [(11)C]-RS 2360 on the other hand indicated specific binding in MAO-A at the earliest time points.
  
  
  CONCLUSIONS
  [(11)C]-RS 2315 displayed a high nonspecific binding and is therefore not suitable for visualization of MAO-A in vivo. [(11)C]-RS 2360 on the other hand has potential for mapping MAO-A since specific binding is demonstrated.
authors.affiliation: Laboratory for Radiopharmacy, Ghent University, 9000 Ghent, Belgium.
authors.forename: Sylvie
authors.initials: S
authors.lastname: De Bruyne
authors.forename: Giuseppe
authors.initials: G
authors.lastname: La Regina
authors.forename: Steven
authors.initials: S
authors.lastname: Staelens
authors.forename: Leonie
authors.initials: L
authors.lastname: Wyffels
authors.forename: Steven
authors.initials: S
authors.lastname: Deleye
authors.forename: Romano
authors.initials: R
authors.lastname: Silvestri
authors.forename: Filip
authors.initials: F
authors.lastname: De Vos
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002250:Carbon Radioisotopes; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D049268:Positron-Emission Tomography / Q000379:methods*; D011758:Pyrroles / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D011786:Quality Control; D011854:Radiochemistry; D051381:Rats
chemical_list: D002250:Carbon Radioisotopes; D008996:Monoamine Oxidase Inhibitors; D011758:Pyrroles; D008995:Monoamine Oxidase