title: N-methylquipazine: carbon-11 labelling of the 5-HT3 agonist and in vivo evaluation of its biodistribution using PET.
abstract: N-Methylquipazine (2-[1-(4-methyl)-piperazinyl)quinoline)) was labelled with carbon-11 by reacting [11C]methyl iodide with the nor-compound, quipazine. Radiochemical conversions were 79 +/- 7%, based on the alkylating agent. The total synthesis time including purification was 40 to 45 min. N-[Methyl-11C]methylquipazine thus synthesized was >99% radiochemically pure, and the specific activity ranged between 12-37 GBq/mumol. Dynamic imaging with PET was used to examine in vivo its distribution in rat and monkey. In rat the organ uptake at intermediate times was: liver > heart > whole brain > or = lung > extracerebral tissue. Brain uptake and wash-out were rapid: A maximum was reached in 2 to 3 min with subsequent decrease to approximately equal to 50% the peak value by 13 min. In monkey the tracer uptake was heterogeneous and high in regions known to contain 5-HT3 receptors but also in regions devoid of these receptors. Tissue kinetics were similar for all regions (initial rapid accumulation with tmax < or = 7 min, followed by slow decrease with all regions approaching the level of the cerebellum at 30 to 35 min). Pretreating with quipazine significantly decreased only the ratio of uptake in the medulla oblongata compared to the cerebellum. Although the nonspecificity of its binding limits the usefulness of N-[methyl-11C]methylquipazine, both its kinetic behavior and the blocking results indicate that a more selective arylpiperazine might prove to be a more attractive tracer for PET studies of 5-HT3 receptors.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Hospital and Institute, Stockholm, Sweden.
authors.forename: J O
authors.initials: JO
authors.lastname: Thorell
authors.forename: S
authors.initials: S
authors.lastname: Stone-Elander
authors.forename: L
authors.initials: L
authors.lastname: Eriksson
authors.forename: M
authors.initials: M
authors.lastname: Ingvar
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D007553:Isotope Labeling; D008252:Macaca fascicularis; D008297:Male; D011814:Quipazine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000032:analysis*; D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists; C109625:N-methylquipazine; D011814:Quipazine