HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) A correction has been published Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gründer, G. Articles by Bartenstein, P. Search for Related Content PubMed PubMed Citation Articles by Gründer, G. Articles by Bartenstein, P.

Quantification of D₂-Like Dopamine Receptors in the Human Brain with ¹⁸F-Desmethoxyfallypride

¹ Department of Psychiatry, University of Mainz, Mainz, Germany
² Department of Nuclear Medicine, University of Mainz, Mainz, Germany
³ Institute of Nuclear Chemistry, University of Mainz, Mainz, Germany
⁴ Division of Nuclear Medicine, Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, Maryland

Substituted benzamides such as ¹¹C-raclopride or ¹²³I-iodobenzamide are selective radiotracers for PET and SPECT imaging of D₂-like dopamine (DA) receptors. ¹⁸F-Desmethoxyfallypride (¹⁸F-DMFP) is a benzamide tracer with the advantage of an ¹⁸F label. We optimized the synthesis and evaluated ¹⁸F-DMFP in PET studies on healthy human volunteers. Methods: The affinity of DMFP for D₂-like DA receptors was characterized in vitro using membrane preparations from rat striatum and the DA receptor ligand ³H-spiperone. PET studies on 10 healthy human volunteers were performed using a whole-body PET scanner after injection of 214 ± 54 MBq (mean ± SD) ¹⁸F-DMFP. Brain images were acquired dynamically over 124 min, and metabolite-corrected plasma activity was used as the input function. Data analysis was performed using several different approaches (compartmental, graphical, equilibrium methods). Results: The mean inhibition constant (K_i) of DMFP was 15 ± 9 nmol/L. In human brain, the striatum-to-cerebellum ratio reached a maximum of about 4 between 60 and 120 min. When specific binding in the striatum was expressed as the difference between binding in the striatum and the cerebellum, it reached a maximum at approximately 60 min after injection and remained almost constant until the end of data acquisition. The ratio of specific striatal to nonspecific cerebellar binding was about 3:1 at 120 min after injection. A small, but significant specific tracer binding could also be detected in the thalamus. Treatment of a schizophrenic patient with a high dose (1,000 mg/d) of another substituted benzamide, amisulpride, resulted in a reduction of specific tracer uptake of about 90% in striatal regions. With regard to measured distribution volumes and binding potentials, there was an excellent agreement between all applied analytic methods. Conclusion: Our study demonstrates that ¹⁸F-DMFP is a highly reliable tracer for PET imaging of D₂-like DA receptors. It offers the major advantage that it can be used independently of an on-site cyclotron within a PET satellite network. Noninvasive analytic methods without blood sampling provide valid measurements of receptor quantities in human striatum. Because of the ¹⁸F label and the favorable imaging properties, ¹⁸F-DMFP could become an efficient substitute for ¹¹C-raclopride in a clinical context.

Key Words: D₂-like dopamine receptors • PET • ¹⁸F-desmethoxyfallypride • caudate nucleus • putamen • thalamus

This article has been cited by other articles:

				A. Heinz, T. Siessmeier, J. Wrase, H. G. Buchholz, G. Grunder, Y. Kumakura, P. Cumming, M. Schreckenberger, M. N. Smolka, F. Rosch, et al. Correlation of Alcohol Craving With Striatal Dopamine Synthesis Capacity and D2/3 Receptor Availability: A Combined [18F]DOPA and [18F]DMFP PET Study in Detoxified Alcoholic Patients Am J Psychiatry, August 1, 2005; 162(8): 1515 - 1520. [Abstract] [Full Text] [PDF]

				T. Siessmeier, Y. Zhou, H.-G. Buchholz, C. Landvogt, I. Vernaleken, M. Piel, R. Schirrmacher, F. Rosch, M. Schreckenberger, D. F. Wong, et al. Parametric Mapping of Binding in Human Brain of D2 Receptor Ligands of Different Affinities J. Nucl. Med., June 1, 2005; 46(6): 964 - 972. [Abstract] [Full Text] [PDF]

				A. Heinz, T. Siessmeier, J. Wrase, D. Hermann, S. Klein, S. M. Grusser-Sinopoli, H. Flor, D. F. Braus, H. G. Buchholz, G. Grunder, et al. Correlation Between Dopamine D2 Receptors in the Ventral Striatum and Central Processing of Alcohol Cues and Craving Am J Psychiatry, October 1, 2004; 161(10): 1783 - 1789. [Abstract] [Full Text] [PDF]