PET examination of [(11)C]5-methyl-6-nitroquipazine, a radioligand for visualization of the serotonin transporter.
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.
Sandell
Johan
J
Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-171 76 Stockholm, Sweden. johan.sandell@pet.uu.se
Halldin
Christer
C
Sovago
Judith
J
Chou
Yuan-Hwa
YH
Gulyás
Balász
B
Yu
Meixiang
M
Emond
Patrick
P
Någren
Kjell
K
Guilloteau
Denis
D
Farde
Lars
L
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
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