Quantification of D2-like dopamine receptors in the human brain with 18F-desmethoxyfallypride
- Publication type:
- Journal article
- Metadata:
-
- 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
Data source: Web of Science (Lite)
- Other metadata sources:
-
- 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
- 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
Data source: 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
Data source: PubMed
- Beziehungen:
- Property of