title: S-[18F]fluoromethyl-(+)-McN5652, a PET tracer for the serotonin transporter: evaluation in rats.
abstract: The [(18)F]fluoromethyl analog of (+)-McN5652 ([(18)F]FMe-McN) for imaging serotonin transporter (SERT) with positron emission tomography (PET) has recently been synthesized. We describe here the biological evaluation of [(18)F]FMe-McN in rats. Biodistribution studies of [(18)F]FMe-McN in rat brain ex vivo after an intravenous injection showed a high accumulation of radioactivity in the regions rich in SERT, such as raphe nuclei, hypothalamus, thalamus, substantia nigra, locus coeruleus, and amygdala. Region-to-cerebellum ratios reached a maximum value of 9 in raphe nuclei within 3.5 h after administration. The specificity and selectivity of [(18)F]FMe-McN binding to SERT was studied by preinjecting blocking doses of serotonin, norepinephrine, and dopamine transporter inhibitors. Fluoxetine, a specific inhibitor for SERT, decreased the specific binding of [(18)F]FMe-McN in raphe nuclei by 91 +/- 4%; in other regions rich in SERT, similar results were obtained. GBR12909 and nisoxetine, selective inhibitors for dopamine transporter (DAT) and norepinephrine transporter (NET), respectively, showed no significant effects on the uptake of [(18)F]FMe-McN. Our studies show that [(18)F]FMe-McN has a clear potential as a tracer for studies with PET of SERT function in humans.
authors.affiliation: MediCity PET Laboratory, Turku PET Centre, Turku, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Marjamäki
authors.forename: Jörg
authors.initials: J
authors.lastname: Zessin
authors.forename: Olli
authors.initials: O
authors.lastname: Eskola
authors.forename: Tove
authors.initials: T
authors.lastname: Grönroos
authors.forename: Merja
authors.initials: M
authors.lastname: Haaparanta
authors.forename: Jörgen
authors.initials: J
authors.lastname: Bergman
authors.forename: Pertti
authors.initials: P
authors.lastname: Lehikoinen
authors.forename: Sarita
authors.initials: S
authors.lastname: Forsback
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
authors.forename: Olof
authors.initials: O
authors.lastname: Solin
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D005462:Fluorine Radioisotopes; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007546:Isoquinolines; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010879:Piperazines / Q000494:pharmacology; D011849:Radioactive Tracers; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D027981:Symporters / Q000037:antagonists & inhibitors; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D005462:Fluorine Radioisotopes; D005473:Fluoxetine; D007546:Isoquinolines; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010879:Piperazines; D011849:Radioactive Tracers; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D027981:Symporters; C493226:Slc6a2 protein, rat; C493216:Slc6a3 protein, rat; C493232:Slc6a4 protein, rat; C011386:nisoxetine; C043425:vanoxerine; C058079:McN 5652