title: Synthesis of [11C]dapoxetine.HCl, a serotonin re-uptake inhibitor: biodistribution in rat and preliminary PET imaging in the monkey.
abstract: [11C]Dapoxetine.HCl, S-(+)-N,N-dimethyl-a-[2-(naphthalenyloxy)ethyl] benzenemethanamine hydrochloride, a potent serotonin re-uptake inhibitor was prepared from its mono-methyl precursor, S-(+)-N-methyl-a-[2-(naphthalenyloxy)ethyl]benzene methanamine hydrochloride. Biodistribution was determined in rats at 5, 30 and 60 min after injection and preliminary PET studies were performed in a Rhesus monkey. 11CH3I was bubbled into a solution of S-(+)-N-methyl-alpha-[2-(naphthalenyloxy)ethyl]benzene methanamine hydrochloride (3.0 mg in DMSO) and the mixture was heated at 110 degrees C for 8 min. [11C]Dapoxetine.HCl was purified by HPLC on a C18 cartridge eluted with MeOH:phosphate buffer, pH 7,2 (75:25) with a 10% yield (end of synthesis). The time required for the synthesis was 40 min, from the end of bombardment. Radiochemical purity of the final product was > 99% and specific activity was routinely > 400 mCi/mumol [EOS]. In the biodistribution studies the highest concentration (%ID/g +/- SEM) of dapoxetine.HCl was detected in lung: 4.56 +/- 0.27 (5 min), 1.28 +/- 0.18 (30 min) and 0.67 +/- 0.04 (60 min). Brain accumulation was 0.76 +/- 0.02 (5 min), 0.46 +/- 0.04 (30 min) and 0.27 +/- 0.01 (60 min). Preliminary PET studies demonstrated significant displaceable binding in the cerebral cortex and subcortical grey matter. These results demonstrate that [11C]dapoxetine.HCl can be prepared in high purity and may be useful for the in vivo evaluation of serotonin re-uptake mechanisms.
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston 02114, USA.
authors.forename: E
authors.initials: E
authors.lastname: Livni
authors.forename: W
authors.initials: W
authors.lastname: Satterlee
authors.forename: R L
authors.initials: RL
authors.lastname: Robey
authors.forename: C A
authors.initials: CA
authors.lastname: Alt
authors.forename: E E
authors.initials: EE
authors.lastname: Van Meter
authors.forename: J W
authors.initials: JW
authors.lastname: Babich
authors.forename: W J
authors.initials: WJ
authors.lastname: Wheeler
authors.forename: D D
authors.initials: DD
authors.lastname: O'Bannon
authors.forename: J H
authors.initials: JH
authors.lastname: Thrall
authors.forename: A J
authors.initials: AJ
authors.lastname: Fischman
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D001596:Benzylamines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes / Q000737:chemistry*; D005260:Female; D007553:Isotope Labeling; D008253:Macaca mulatta; D008297:Male; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D000928:Antidepressive Agents; D001596:Benzylamines; D002250:Carbon Radioisotopes; D009281:Naphthalenes; D017367:Selective Serotonin Reuptake Inhibitors; C080598:dapoxetine