title: Autoradiographic imaging of the serotonin transporter in the brain of rats and pigs using S-([18F]fluoromethyl)-(+)-McN5652.
abstract: The [18F]fluoromethyl analogue of (+)-McN5652 ([18F]FMe-McN) has recently been developed as a radioligand for imaging the neuronal serotonin transporter (SERT) with positron emission tomography (PET). We describe here the autoradiographic evaluation of [18F]FMe-McN in the brain of rats and pigs. Autoradiographic studies of [18F]FMe-McN performed on rat and pig brain in vitro showed a high accumulation of radioactivity in the regions rich in SERT, such as amygdala, hypothalamus, superficial gray layer of the superior colliculus, various nuclei of thalamus and substantia nigra. The binding of [18F]FMe-McN was reduced by citalopram, a highly selective inhibitor for SERT. Similar regional specific binding densities of [18F]FMe-McN were observed in both species. The regional distribution and specific binding of this radiotracer correlates well with the distribution and regional brain binding of [3H]citalopram. Region-to-cerebellum ratios of [18F]FMe-McN in vitro reached a maximum value of 20.6 in the rat and 14.5 in the pig. In addition, ex vivo autoradiography of the rat brain was performed 90 min after i.v. administration of [18F]FMe-McN. The highest regional uptake of [18F]FMe-McN was observed in the hypothalamic area, substantia nigra and amygdaloid area. There is a high correlation between the in vitro and in vivo binding. The region-to-cerebellum ratio in vivo reached a maximum value of 5.1 in the substantia nigra, the highest yet reported for an 18F-labelled SERT tracer in vivo in this region. Furthermore, the distribution volume of [18F]FMe-McN calculated from the PET data in various regions of the porcine brain is highly correlated with the SERT density as determined by in vitro autoradiography with [3H]citalopram. Thus, [18F]FMe-McN has a clear potential as a radiotracer for studies of the SERT distribution in man with PET.
authors.affiliation: Institut für Bioanorganische und Radiopharmazeutische Chemie, PF 510119, 01314 Dresden, Germany. m.kretzschmar@fz-rossendorf.de
authors.forename: Marion
authors.initials: M
authors.lastname: Kretzschmar
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
authors.forename: Jörg
authors.initials: J
authors.lastname: Zessin
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
authors.forename: Ralf
authors.initials: R
authors.lastname: Bergmann
authors.forename: Bernd
authors.initials: B
authors.lastname: Johannsen
mesh_terms: D000818:Animals; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism*; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011485:Protein Binding / Q000502:physiology; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D050486:Serotonin Plasma Membrane Transport Proteins; D013552:Swine
chemical_list: D002352:Carrier Proteins; D005462:Fluorine Radioisotopes; D007546:Isoquinolines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; C058079:McN 5652