title: Imaging of the brain serotonin transporters (SERT) with 18F-labelled fluoromethyl-McN5652 and PET in humans.
abstract: OBJECTIVE
  [(11)C]DASB is currently the most frequently used highly selective radiotracer for visualization and quantification of central SERT. Its use, however, is hampered by the short half-life of (11)C, the moderate cortical test-retest reliability, and the lack of quantifying endogenous serotonin. Labelling with (18)F allows in principle longer acquisition times for kinetic analysis in brain tissue and may provide higher sensitivity. The aim of our study was to firstly use the new highly SERT-selective (18)F-labelled fluoromethyl analogue of (+)-McN5652 ((+)-[(18)F]FMe-McN5652) in humans and to evaluate its potential for SERT quantification.
  
  
  METHODS
  The PET data from five healthy volunteers (three men, two women, age 39 ± 10 years) coregistered with individual MRI scans were semiquantitatively assessed by volume-of-interest analysis using the software package PMOD. Rate constants and total distribution volumes (V (T)) were calculated using a two-tissue compartment model and arterial input function measurements were corrected for metabolite/plasma data. Standardized uptake region-to-cerebellum ratios as a measure of specific radiotracer accumulation were compared with those of a [(11)C]DASB PET dataset from 21 healthy subjects (10 men, 11 women, age 38 ± 8 years).
  
  
  RESULTS
  The two-tissue compartment model provided adequate fits to the data. Estimates of total distribution volume (V (T)) demonstrated good identifiability based on the coefficients of variation (COV) for the volumes of interest in SERT-rich and cortical areas (COV V (T) <10%). Compared with [(11)C]DASB PET, there was a tendency to lower mean uptake values in (+)-[(18)F]FMe-McN5652 PET; however, the standard deviation was also somewhat lower. Altogether, cerebral (+)-[(18)F]FMe-McN5652 uptake corresponded well with the known SERT distribution in humans.
  
  
  CONCLUSIONS
  The results showed that (+)-[(18)F]FMe-McN5652 is also suitable for in vivo quantification of SERT with PET. Because of the long half-life of (18)F, the widespread use within a satellite concept seems feasible.
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany. swen.hesse@medizin.uni-leipzig.de
authors.forename: Swen
authors.initials: S
authors.lastname: Hesse
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
authors.forename: Peter
authors.initials: P
authors.lastname: Mäding
authors.forename: Georg-Alexander
authors.initials: GA
authors.lastname: Becker
authors.forename: Marianne
authors.initials: M
authors.lastname: Patt
authors.forename: Anita
authors.initials: A
authors.lastname: Seese
authors.forename: Dietlind
authors.initials: D
authors.lastname: Sorger
authors.forename: Jörg
authors.initials: J
authors.lastname: Zessin
authors.forename: Philipp M
authors.initials: PM
authors.lastname: Meyer
authors.forename: Donald
authors.initials: D
authors.lastname: Lobsien
authors.forename: Sven
authors.initials: S
authors.lastname: Laudi
authors.forename: Bernd
authors.initials: B
authors.lastname: Habermann
authors.forename: Frank
authors.initials: F
authors.lastname: Füchtner
authors.forename: Julia
authors.initials: J
authors.lastname: Luthardt
authors.forename: Anke
authors.initials: A
authors.lastname: Bresch
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
authors.forename: Osama
authors.initials: O
authors.lastname: Sabri
mesh_terms: D000328:Adult; D001665:Binding Sites; D001692:Biological Transport; D001798:Blood Proteins / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D007546:Isoquinolines / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D049268:Positron-Emission Tomography / Q000009:adverse effects / Q000379:methods* / Q000592:standards; D012015:Reference Standards; D012449:Safety; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D005462:Fluorine Radioisotopes; D007546:Isoquinolines; D050486:Serotonin Plasma Membrane Transport Proteins; C058079:McN 5652