title: Characterization of [123I]FP-CIT binding to the dopamine transporter in the striatum of tree shrews by quantitative in vitro autoradiography.
abstract: OBJECTIVE
  Aim of this study was to quantify the binding of [(123) I]FP-CIT in striatum of healthy tree shrews. [(123) I]FP-CIT is widely used in clinical SPECT imaging to reveal nigrostriatal degeneration in aid of the diagnosis of clinically uncertain parkinsonian syndromes. Despite its wide clinical use, the saturation binding parameters of [(123) I]FP-CIT for the dopamine transporter (DAT) have not yet been determined in any mammalian brain. Tree shrews are genetically and neuroanatomically more similar to humans than are rodents and might therefore be a valuable animal model for research of neurological disorders involving brain dopamine.
  
  
  METHODS
  Quantitative in vitro autoradiography with [(123) I]FP-CIT was performed with brains of healthy tree shrews and, for comparison, brains of healthy rats. Dopamine D2/3 receptor autoradiography with [(3) H]raclopride was also performed.
  
  
  RESULTS
  Saturation analysis revealed high specificity of [(123) I]FP-CIT for DAT in the striatum with considerably higher affinity in tree shrews than in rats (KD  = 10.3 versus 36.4 nM). The density of DAT binding sites also was higher in tree shrews than in rats (Bmax  = 2499 versus 1495 pmol/g wet weight (ww)). [(3) H]raclopride revealed D2/3 receptors in the tree shrew striatum with about the same density as in rats (Bmax  = 78.4 versus 84.1 pmol/g ww), but with slightly lower affinity in tree shrews (KD  = 1.27 versus 0.59 nM).
  
  
  CONCLUSIONS
  The higher affinity in combination with the higher abundance of DAT binding sites compared to rat striatum predicts substantially higher binding of [(123) I]FP-CIT in SPECT studies of living tree shrews.
authors.affiliation: Forschungszentrum Jülich GmbH - Institute of Neuroscience and Medicine, Jülich, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Geisler
authors.affiliation: Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Beindorff
authors.affiliation: Forschungszentrum Jülich GmbH - Institute of Neuroscience and Medicine, Jülich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Cremer
authors.affiliation: German Primate Center, Göttingen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hoffmann
authors.affiliation: Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Brenner
authors.affiliation: Department of Nuclear Medicine, Friedrich-Alexander University, Erlangen/Nürnberg, Germany.|Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
authors.affiliation: Department of Nuclear Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Philipp T
authors.initials: PT
authors.lastname: Meyer
authors.affiliation: Forschungszentrum Jülich GmbH - Institute of Neuroscience and Medicine, Jülich, Germany.|Department of Nuclear Medicine, University of Aachen, Aachen, Germany.
authors.forename: Karl-Josef
authors.initials: KJ
authors.lastname: Langen
authors.affiliation: German Primate Center, Göttingen, Germany.|Department of Neurology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Fuchs
authors.affiliation: Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Buchert
mesh_terms: D000818:Animals; D001345:Autoradiography; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D020891:Raclopride / Q000493:pharmacokinetics; D051381:Rats; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes / Q000493:pharmacokinetics*; D014418:Tupaiidae
chemical_list: D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D020891:Raclopride
keywords: [123I]FP-CIT; autoradiography; dissociation constant; dopamine receptor; dopamine transporter; mammalian brain; raclopride; tree shrew; tupaia