Quantification of D2-like dopamine receptors in the human brain with 18F-desmethoxyfallypride

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • G Gründer
  • T Siessmeier
  • M Piel
  • I Vernaleken
  • HG Buchholz
  • Y Zhou
  • C Hiemke
  • DF Wong
  • F Rösch
  • P Bartenstein
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000180276500037&DestLinkType=FullRecord&DestApp=WOS_CPL
eISSN
1535-5667
Externe Identifier
  • Clarivate Analytics Document Solution ID: 633HJ
  • PubMed Identifier: 12515884
ISSN
0161-5505
Ausgabe der Veröffentlichung
1
Zeitschrift
JOURNAL OF NUCLEAR MEDICINE
Schlüsselwörter
  • D-2-like dopamine receptors
  • PET
  • F-18-desmethoxyfallypride
  • caudate nucleus
  • putamen
  • thalamus
Paginierung
109 - 116
Datum der Veröffentlichung
2003
Status
Published
Titel
Quantification of D<sub>2</sub>-like dopamine receptors in the human brain with <SUP>18</SUP>F-desmethoxyfallypride
Sub types
  • Article
Ausgabe der Zeitschrift
44

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Abstract
<h4>Unlabelled</h4>Substituted benzamides such as (11)C-raclopride or (123)I-iodobenzamide are selective radiotracers for PET and SPECT imaging of D(2)-like dopamine (DA) receptors. (18)F-Desmethoxyfallypride ((18)F-DMFP) is a benzamide tracer with the advantage of an (18)F label. We optimized the synthesis and evaluated (18)F-DMFP in PET studies on healthy human volunteers.<h4>Methods</h4>The affinity of DMFP for D(2)-like DA receptors was characterized in vitro using membrane preparations from rat striatum and the DA receptor ligand (3)H-spiperone. PET studies on 10 healthy human volunteers were performed using a whole-body PET scanner after injection of 214 +/- 54 MBq (mean +/- SD) (18)F-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).<h4>Results</h4>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.<h4>Conclusion</h4>Our study demonstrates that (18)F-DMFP is a highly reliable tracer for PET imaging of D(2)-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 (18)F label and the favorable imaging properties, (18)F-DMFP could become an efficient substitute for (11)C-raclopride in a clinical context.
Addresses
  • Department of Psychiatry, University of Mainz, Mainz, Germany. gruender@mail.uni-mainz.de
Autoren
  • Gerhard Gründer
  • Thomas Siessmeier
  • Markus Piel
  • Ingo Vernaleken
  • Hans-Georg Buchholz
  • Yun Zhou
  • Christoph Hiemke
  • Dean F Wong
  • Frank Rösch
  • Peter Bartenstein
eISSN
1535-5667
Externe Identifier
  • PubMed Identifier: 12515884
Funding acknowledgements
  • NIDA NIH HHS: R01 DA11080
  • NINDS NIH HHS: K24 NS389279
  • NIMH NIH HHS: R01 MH4282
  • NIDA NIH HHS: R01 DA 094821
  • NIAAA NIH HHS: R01 AA1283
Open access
false
ISSN
0161-5505
Ausgabe der Veröffentlichung
1
Zeitschrift
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Schlüsselwörter
  • Brain
  • Animals
  • Humans
  • Rats
  • Salicylamides
  • Receptors, Dopamine D2
  • Radiopharmaceuticals
  • Tomography, Emission-Computed
  • Schizophrenia
  • Tissue Distribution
  • Models, Biological
  • Adult
  • Male
  • In Vitro Techniques
Sprache
eng
Medium
Print
Paginierung
109 - 116
Datum der Veröffentlichung
2003
Status
Published
Datum der Datenerfassung
2003
Titel
Quantification of D2-like dopamine receptors in the human brain with 18F-desmethoxyfallypride.
Sub types
  • Comparative Study
  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
44

Datenquelle: Europe PubMed Central

Abstract
UNLABELLED: Substituted benzamides such as (11)C-raclopride or (123)I-iodobenzamide are selective radiotracers for PET and SPECT imaging of D(2)-like dopamine (DA) receptors. (18)F-Desmethoxyfallypride ((18)F-DMFP) is a benzamide tracer with the advantage of an (18)F label. We optimized the synthesis and evaluated (18)F-DMFP in PET studies on healthy human volunteers. METHODS: The affinity of DMFP for D(2)-like DA receptors was characterized in vitro using membrane preparations from rat striatum and the DA receptor ligand (3)H-spiperone. PET studies on 10 healthy human volunteers were performed using a whole-body PET scanner after injection of 214 +/- 54 MBq (mean +/- SD) (18)F-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 (18)F-DMFP is a highly reliable tracer for PET imaging of D(2)-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 (18)F label and the favorable imaging properties, (18)F-DMFP could become an efficient substitute for (11)C-raclopride in a clinical context.
Autoren
  • Gerhard Gründer
  • Thomas Siessmeier
  • Markus Piel
  • Ingo Vernaleken
  • Hans-Georg Buchholz
  • Yun Zhou
  • Christoph Hiemke
  • Dean F Wong
  • Frank Rösch
  • Peter Bartenstein
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/12515884
Funding acknowledgements
  • NINDS NIH HHS: K24 NS389279
  • NIAAA NIH HHS: R01 AA1283
  • NIDA NIH HHS: R01 DA 094821
  • NIDA NIH HHS: R01 DA11080
  • NIMH NIH HHS: R01 MH4282
ISSN
0161-5505
Ausgabe der Veröffentlichung
1
Zeitschrift
J Nucl Med
Schlüsselwörter
  • Adult
  • Animals
  • Brain
  • Humans
  • In Vitro Techniques
  • Male
  • Models, Biological
  • Radiopharmaceuticals
  • Rats
  • Receptors, Dopamine D2
  • Salicylamides
  • Schizophrenia
  • Tissue Distribution
  • Tomography, Emission-Computed
Sprache
eng
Country
United States
Paginierung
109 - 116
Datum der Veröffentlichung
2003
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2003
Titel
Quantification of D2-like dopamine receptors in the human brain with 18F-desmethoxyfallypride.
Sub types
  • Clinical Trial
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
Ausgabe der Zeitschrift
44

Datenquelle: PubMed

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