title: In vivo biodistribution of a radiotracer for imaging serotonin-1A receptor sites with PET:[11C]LY274601.
abstract: LY274601 [R-(+)8-thiomethyl-2-(di-n-propyl-amino)tetralin], a full agonist of the 5-HT1A receptor with high affinity and selectivity, was labeled with 11C and 3H, and its in vivo behavior was studied to evaluate [11C]LY274601 as a PET radiotracer for imaging 5-HT1A receptor sites in living brain. Following intravenous tail injection into mice, [11C]LY274601 showed high blood-brain barrier permeability and accumulated in regions known to have high densities of 5-HT1A receptor sites such as the brain stem including the raphe nuclei. The binding of the radiotracer in target tissues is blocked by pre-injection of the 5-HT1A receptor selective ligand 8-OH-DPAT (1 mg/kg, s.c.), suggesting that the binding is specific to 5-HT1A receptor sites. Using ex vivo autoradiography, the target tissues such as hippocampus CA1-4 fields, piriform cortex, dorsal raphe nucleus and lateral septum were visualized as hot spots. These tissues were observed to have binding 2-2.7 times greater than the cerebellum. The distribution of the radiotracer agrees well with the distribution of 5-HT1A receptors revealed by in vitro autoradiography with [3H]8-OH-DPAT. However, the radiotracer was metabolized quickly and cleared from target tissues with a half life of approximately 15 min. [11C]LY274601 showed high non-specific binding in regions with low number of 5-HT1A receptor sites such as cerebellum.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York Psychiatric Institute, NY 10032, USA.
authors.forename: M
authors.initials: M
authors.lastname: Suehiro
authors.forename: M
authors.initials: M
authors.lastname: Underwood
authors.forename: V
authors.initials: V
authors.lastname: Arango
authors.forename: T S
authors.initials: TS
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Kassir
authors.forename: M
authors.initials: M
authors.lastname: Bakalian
authors.forename: T
authors.initials: T
authors.lastname: Yatabe
authors.forename: M
authors.initials: M
authors.lastname: Pratap
authors.forename: R L
authors.initials: RL
authors.lastname: Van Heertum
authors.forename: J J
authors.initials: JJ
authors.lastname: Mann
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D051379:Mice; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods
chemical_list: C115409:LY 274601; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin