title: PET examination of [(11)C]5-methyl-6-nitroquipazine, a radioligand for visualization of the serotonin transporter.
abstract: Radiohalogenated 5-halo-6-nitroquipazine analogues have been shown to be potential radioligands for visualization of the serotonin transporter (5-HTT) with PET and SPECT. In the present study a methylated analogue, 5-methyl-6-nitroquipazine (MNQP), was radiolabeled with carbon-11 in a two step reaction via a palladium catalyzed cross coupling reaction between N-t-BOC-protected 5-tributylstannyl-6-nitroquipazine and [(11)C]methyl iodide as key step. [(11)C]MNQP was examined in the cynomolgus monkey brain with positron emission tomography (PET) and the appearance of labeled metabolites in monkey plasma was measured with gradient HPLC. Radioactivity increased continuously in all brain regions during the 90 minutes acquisition time. Highest accumulation of radioactivity was observed in the thalamus and brainstem, regions with a known high density of 5-HTT. The calculated ratios between the thalamus and brainstem to the 5-HTT poor cerebellum were 1.5 and 1.3-1.4, respectively, 80 minutes after radioligand injection. Pretreatment with citalopram prior to the PET measurement markedly reduced the binding in the thalamus and the brainstem. At 15 and 30 minutes after injection of [(11)C]MNQP approximately 90% and 60%, respectively, of radioactivity in plasma represented unchanged radioligand. The slow kinetics and moderate ratios recorded however, may limit its use as a PET radioligand for quantitative studies of the serotonin transporter with PET.
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-171 76 Stockholm, Sweden. johan.sandell@pet.uu.se
authors.forename: Johan
authors.initials: J
authors.lastname: Sandell
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
authors.forename: Judith
authors.initials: J
authors.lastname: Sovago
authors.forename: Yuan-Hwa
authors.initials: YH
authors.lastname: Chou
authors.forename: Balász
authors.initials: B
authors.lastname: Gulyás
authors.forename: Meixiang
authors.initials: M
authors.lastname: Yu
authors.forename: Patrick
authors.initials: P
authors.lastname: Emond
authors.forename: Kjell
authors.initials: K
authors.lastname: Någren
authors.forename: Denis
authors.initials: D
authors.lastname: Guilloteau
authors.forename: Lars
authors.initials: L
authors.lastname: Farde
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism*; D000882:Haplorhini; D008562:Membrane Glycoproteins / Q000097:blood / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011814:Quipazine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D050486:Serotonin Plasma Membrane Transport Proteins; D014055:Tomography, Emission-Computed
chemical_list: C471420:5-methyl-6-nitroquipazine; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D011814:Quipazine