title: Parametric mapping of binding in human brain of D2 receptor ligands of different affinities.
abstract: (11)C-Raclopride has been widely used for PET studies of dopamine D(2/3) receptors in human brain. The long half-life of (18)F may impart advantages to the novel moderate-affinity benzamide (18)F-desmethoxyfallypride and its high-affinity congener (18)F-fallypride for competition studies and for detection of extrastriatal binding. However, the in vivo kinetics of these compounds and the quantification approaches for parametric mapping of their specific bindings have not been systematically compared.
  
  
  METHODS
  Dynamic emission recordings of the 3 tracers were obtained in groups of healthy subjects. A conventional model, graphical analysis using metabolite-corrected arterial inputs, and models with reference tissue inputs were used to calculate voxelwise parametric maps of the equilibrium distribution volume (V(d)) and the binding potential (BP) of the 3 radioligands in brain. To test for bias, voxelwise kinetic results were compared with those obtained by volume-of-interest (VOI) analysis.
  
  
  RESULTS
  The V(d) and BP estimates obtained by VOI analysis did not differ from the mean of voxelwise estimates in the same striatal volumes. In striatum, the mean (18)F-desmethoxyfallypride BP ranged from 1.9 to 2.5, whereas the mean (11)C-raclopride BP ranged from 3 to 4, depending on the method used for calculation. In contrast, the mean BP of (18)F-fallypride ranged from 16 to 27 in striatum and could also be readily quantified in the thalamus.
  
  
  CONCLUSIONS
  Reference tissue methods for the voxelwise calculation of binding parameters are suitable for parametric mapping of the 3 dopamine D(2/3) receptor ligands.
authors.affiliation: Department of Nuclear Medicine, University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany. siessmeier@nuklear.klinik.uni-mainz.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Siessmeier
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Buchholz
authors.forename: Christian
authors.initials: C
authors.lastname: Landvogt
authors.forename: Ingo
authors.initials: I
authors.lastname: Vernaleken
authors.forename: Markus
authors.initials: M
authors.lastname: Piel
authors.forename: Ralf
authors.initials: R
authors.lastname: Schirrmacher
authors.forename: Frank
authors.initials: F
authors.lastname: Rösch
authors.forename: Mathias
authors.initials: M
authors.lastname: Schreckenberger
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
mesh_terms: D000328:Adult; D001549:Benzamides / Q000378:metabolism* / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008024:Ligands; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011759:Pyrrolidines / Q000378:metabolism* / Q000493:pharmacokinetics; D020891:Raclopride / Q000378:metabolism* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000378:metabolism* / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D012457:Salicylamides / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D001549:Benzamides; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D008024:Ligands; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C100958:desmethoxyfallypride; D020891:Raclopride