Parametric mapping of binding in human brain of D2 receptor ligands of different affinities.
(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.
Siessmeier
Thomas
T
Department of Nuclear Medicine, University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany. siessmeier@nuklear.klinik.uni-mainz.de
Zhou
Yun
Y
Buchholz
Hans-Georg
HG
Landvogt
Christian
C
Vernaleken
Ingo
I
Piel
Markus
M
Schirrmacher
Ralf
R
Rösch
Frank
F
Schreckenberger
Mathias
M
Wong
Dean F
DF
Cumming
Paul
P
Gründer
Gerhard
G
Bartenstein
Peter
P
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
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