title: A radiometabolite study of the serotonin transporter PET radioligand [(11)C]MADAM.
abstract: BACKGROUND
  (11)C]MADAM is a radioligand suitable for PET studies of the serotonin transporter (SERT). Metabolite analysis in human and non-human plasma samples using HPLC separation has shown that [(11)C]MADAM was rapidly metabolized. A possible metabolic pathway is the S-oxidation which could lead to SOMADAM and SO2MADAM. In vitro evaluation of these two potential metabolites has shown that SOMADAM exhibited a good affinity for SERT and a good selectivity for SERT over NET and DAT.
  
  
  METHODS
  Comparative PET imaging studies in non-human primate brain with [(11)C]MADAM and [(11)C]SOMADAM were carried out, and plasma samples were analyzed using reverse phase HPLC. We have explored the metabolism of [(11)C]MADAM in rat brain with a view to understand its possible interference for brain imaging with PET.
  
  
  RESULTS
  PET imaging studies in non-human primate brain using [(11)C]SOMADAM indicated that this tracer does not bind with high amounts to brain regions known to be rich in SERT. The fraction of [(11)C]SOMADAM in non-human primate plasma was approximately 5% at 4min and 1% at 15min after [(11)C]MADAM injection. HPLC analysis of brain sample after [(11)C]MADAM injection to rats demonstrated that [(11)C]SOMADAM was not detected in the brain.
  
  
  CONCLUSIONS
  (11)C]SOMADAM is not superior over [(11)C]MADAM as a SERT PET radioligand. Nevertheless, [(11)C]SOMADAM has been identified as a minor labeled metabolite of [(11)C]MADAM measured in monkey plasma. [(11)C]SOMADAM was not detected in rat brain.
authors.affiliation: CEA, DSV/I2BM, LDM-TEP Group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen Cedex, France; Université de Caen Basse-Normandie, Caen, France; CNRS, UMR ISTCT 6301, LDM-TEP Group, GIP Cyceron, Caen, France; Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry, SE-171 76 Stockholm, Sweden. Electronic address: gourand@cyceron.fr.
authors.forename: F
authors.initials: F
authors.lastname: Gourand
authors.affiliation: INSERM U930- Université François Rabelais de Tours, CHRU de Tours, Hopital Bretonneau, 2 boulevard Tonnellé, 37044 Tours, France.
authors.forename: P
authors.initials: P
authors.lastname: Emond
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry, SE-171 76 Stockholm, Sweden.
authors.forename: J P
authors.initials: JP
authors.lastname: Bergström
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry, SE-171 76 Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Takano
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry, SE-171 76 Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Gulyás
authors.affiliation: INSERM U930- Université François Rabelais de Tours, CHRU de Tours, Hopital Bretonneau, 2 boulevard Tonnellé, 37044 Tours, France.
authors.forename: D
authors.initials: D
authors.lastname: Guilloteau
authors.affiliation: CEA, DSV/I2BM, LDM-TEP Group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen Cedex, France; Université de Caen Basse-Normandie, Caen, France; CNRS, UMR ISTCT 6301, LDM-TEP Group, GIP Cyceron, Caen, France.
authors.forename: L
authors.initials: L
authors.lastname: Barré
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry, SE-171 76 Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Halldin
mesh_terms: D000818:Animals; D016477:Artifacts; D001596:Benzylamines / Q000737:chemistry / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006801:Humans; D008024:Ligands; D008252:Macaca fascicularis; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*
chemical_list: D001596:Benzylamines; D008024:Ligands; C470437:N,N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: MADAM; Metabolism; Positron emission tomography; Serotonin transporter