Parametric mapping of binding in human brain of D2 receptor ligands of different affinities

Thomas Siessmeier, Yun Zhou, Hans Georg Buchholz, Christian Landvogt, Ingo Vernaleken, Markus Piel, Ralf Schirrmacher, Frank Rösch, Mathias Schreckenberger, Dean Foster Wong, Paul Cumming, Gerhard Gründer, Peter Bartenstein

Research output: Contribution to journalArticle

Abstract

11C-Raclopride has been widely used for PET studies of dopamine D2/3 receptors in human brain. The long half-life of 18F may impart advantages to the novel moderate-affinity benzamide 18F-desmethoxyfallypride and its high-affinity congener 18F-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 (Vd) 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 Vd 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 18F-desmethoxyfallypride BP ranged from 1.9 to 2.5, whereas the mean 11C-raclopride BP ranged from 3 to 4, depending on the method used for calculation. In contrast, the mean BP of 18F-fallypride ranged from 16 to 27 in striatum and could also be readily quantified in the thalamus. Conclusion: Reference tissue methods for the voxelwise calculation of binding parameters are suitable for parametric mapping of the 3 dopamine D2/3 receptor ligands.

Original languageEnglish (US)
Pages (from-to)964-972
Number of pages9
JournalJournal of Nuclear Medicine
Volume46
Issue number6
StatePublished - 2005

Fingerprint

Raclopride
Dopamine D2 Receptors
Ligands
Brain
Corpus Striatum
Thalamus
Half-Life
Healthy Volunteers
N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide
desmethoxyfallypride
benzamide

Keywords

  • Binding potential
  • Desmethoxyfallypride
  • Fallypride
  • Parametric
  • Quantification
  • Raclopride

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Siessmeier, T., Zhou, Y., Buchholz, H. G., Landvogt, C., Vernaleken, I., Piel, M., ... Bartenstein, P. (2005). Parametric mapping of binding in human brain of D2 receptor ligands of different affinities. Journal of Nuclear Medicine, 46(6), 964-972.

Parametric mapping of binding in human brain of D2 receptor ligands of different affinities. / Siessmeier, Thomas; Zhou, Yun; Buchholz, Hans Georg; Landvogt, Christian; Vernaleken, Ingo; Piel, Markus; Schirrmacher, Ralf; Rösch, Frank; Schreckenberger, Mathias; Wong, Dean Foster; Cumming, Paul; Gründer, Gerhard; Bartenstein, Peter.

In: Journal of Nuclear Medicine, Vol. 46, No. 6, 2005, p. 964-972.

Research output: Contribution to journalArticle

Siessmeier, T, Zhou, Y, Buchholz, HG, Landvogt, C, Vernaleken, I, Piel, M, Schirrmacher, R, Rösch, F, Schreckenberger, M, Wong, DF, Cumming, P, Gründer, G & Bartenstein, P 2005, 'Parametric mapping of binding in human brain of D2 receptor ligands of different affinities', Journal of Nuclear Medicine, vol. 46, no. 6, pp. 964-972.
Siessmeier T, Zhou Y, Buchholz HG, Landvogt C, Vernaleken I, Piel M et al. Parametric mapping of binding in human brain of D2 receptor ligands of different affinities. Journal of Nuclear Medicine. 2005;46(6):964-972.
Siessmeier, Thomas ; Zhou, Yun ; Buchholz, Hans Georg ; Landvogt, Christian ; Vernaleken, Ingo ; Piel, Markus ; Schirrmacher, Ralf ; Rösch, Frank ; Schreckenberger, Mathias ; Wong, Dean Foster ; Cumming, Paul ; Gründer, Gerhard ; Bartenstein, Peter. / Parametric mapping of binding in human brain of D2 receptor ligands of different affinities. In: Journal of Nuclear Medicine. 2005 ; Vol. 46, No. 6. pp. 964-972.
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abstract = "11C-Raclopride has been widely used for PET studies of dopamine D2/3 receptors in human brain. The long half-life of 18F may impart advantages to the novel moderate-affinity benzamide 18F-desmethoxyfallypride and its high-affinity congener 18F-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 (Vd) 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 Vd 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 18F-desmethoxyfallypride BP ranged from 1.9 to 2.5, whereas the mean 11C-raclopride BP ranged from 3 to 4, depending on the method used for calculation. In contrast, the mean BP of 18F-fallypride ranged from 16 to 27 in striatum and could also be readily quantified in the thalamus. Conclusion: Reference tissue methods for the voxelwise calculation of binding parameters are suitable for parametric mapping of the 3 dopamine D2/3 receptor ligands.",
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AU - Siessmeier, Thomas

AU - Zhou, Yun

AU - Buchholz, Hans Georg

AU - Landvogt, Christian

AU - Vernaleken, Ingo

AU - Piel, Markus

AU - Schirrmacher, Ralf

AU - Rösch, Frank

AU - Schreckenberger, Mathias

AU - Wong, Dean Foster

AU - Cumming, Paul

AU - Gründer, Gerhard

AU - Bartenstein, Peter

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N2 - 11C-Raclopride has been widely used for PET studies of dopamine D2/3 receptors in human brain. The long half-life of 18F may impart advantages to the novel moderate-affinity benzamide 18F-desmethoxyfallypride and its high-affinity congener 18F-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 (Vd) 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 Vd 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 18F-desmethoxyfallypride BP ranged from 1.9 to 2.5, whereas the mean 11C-raclopride BP ranged from 3 to 4, depending on the method used for calculation. In contrast, the mean BP of 18F-fallypride ranged from 16 to 27 in striatum and could also be readily quantified in the thalamus. Conclusion: Reference tissue methods for the voxelwise calculation of binding parameters are suitable for parametric mapping of the 3 dopamine D2/3 receptor ligands.

AB - 11C-Raclopride has been widely used for PET studies of dopamine D2/3 receptors in human brain. The long half-life of 18F may impart advantages to the novel moderate-affinity benzamide 18F-desmethoxyfallypride and its high-affinity congener 18F-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 (Vd) 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 Vd 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 18F-desmethoxyfallypride BP ranged from 1.9 to 2.5, whereas the mean 11C-raclopride BP ranged from 3 to 4, depending on the method used for calculation. In contrast, the mean BP of 18F-fallypride ranged from 16 to 27 in striatum and could also be readily quantified in the thalamus. Conclusion: Reference tissue methods for the voxelwise calculation of binding parameters are suitable for parametric mapping of the 3 dopamine D2/3 receptor ligands.

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