18F-labeling and evaluation of novel MDL 100907 derivatives as potential 5-HT2A antagonists for molecular imaging
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Fabian Debus
- Matthias M Herth
- Markus Piel
- Hans-Georg Buchholz
- Nicole Bausbacher
- Vasko Kramer
- Hartmut Lueddens
- Frank Roesch
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000277701900013&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.nucmedbio.2010.02.002
- eISSN
- 1872-9614
- Externe Identifier
- Clarivate Analytics Document Solution ID: 596RD
- PubMed Identifier: 20447561
- ISSN
- 0969-8051
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- NUCLEAR MEDICINE AND BIOLOGY
- Schlüsselwörter
- MDL 100907
- MH.MZ
- PET
- Fluorine-18
- 5-HT2A receptor
- Paginierung
- 487 - 495
- Datum der Veröffentlichung
- 2010
- Status
- Published
- Titel
- <SUP>18</SUP>F-Labeling and evaluation of novel MDL 100907 derivatives as potential 5-HT2A antagonists for molecular imaging
- Sub types
- Article
- Ausgabe der Zeitschrift
- 37
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Fabian Debus
- Matthias M Herth
- Markus Piel
- Hans-Georg Buchholz
- Nicole Bausbacher
- Vasko Kramer
- Hartmut Lüddens
- Frank Rösch
- DOI
- 10.1016/j.nucmedbio.2010.02.002
- ISSN
- 0969-8051
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Nuclear Medicine and Biology
- Sprache
- en
- Paginierung
- 487 - 495
- Datum der Veröffentlichung
- 2010
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.nucmedbio.2010.02.002
- Datum der Datenerfassung
- 2018
- Titel
- 18F-Labeling and evaluation of novel MDL 100907 derivatives as potential 5-HT2A antagonists for molecular imaging
- Ausgabe der Zeitschrift
- 37
Data source: Crossref
- Abstract
- <h4>Introduction</h4>The serotonergic system, especially the 5-HT2A receptor, is involved in various diseases and conditions. It is a very interesting target for medicinal applications.<h4>Methods</h4>Two novel 5-HT2A tracers, namely, [(18)F]DD-1 and the enantiomeric pure (R)-[(18)F]MH.MZ, were radiolabeled by (18)F-fluoroalkylation of the corresponding desmethyl analogue. In vitro binding autoradiography on rat brain slices was performed to test the affinity and selectivity of these tracers. Moreover, first microPET experiments of (R)-[(18)F]MH.MZ were carried out in Sprague-Dawley rats.<h4>Results</h4>[(18)F]DD-1 (K(i)=3.23 nM) and (R)-[(18)F]MH.MZ (K(i)=0.72 nM) were (18)F-fluoroalkylated by the secondary synthon [(18)F]FETos in a radiochemical yield (RCY) of >70%. The final formulation for both tracers took no longer than 100 min with an overall RCY of approximately 40%. It provided [(18)F]tracers with a purity >96% and a typical specific activity of 25-35 GBq/mumol. Autoradiographic images of (R)-[(18)F]MH.MZ (5) and [(18)F]DD-1 (4) showed excellent visualization and selectivity of the 5-HT2A receptor for (R)-[(18)F]MH.MZ and less specific binding for [(18)F]DD-1. The binding potential (BP) of (R)-[(18)F]MH.MZ was determined to be 2.6 in the frontal cortex and 2.2 in the cortex (n=4), whereas the cortex-to-cerebellum ratio was determined to be 3.2 at steady state (n=4). Cortex-to-cerebellum ratios of (R)-[(18)F]MH.MZ were almost twice as much as compared with the racemic [(18)F]MH.MZ. Thereby, equal levels of specific activities were used. High uptake could be demonstrated in cortex regions.<h4>Conclusion</h4>Labeling of both novel tracers was carried out in high RCY. Autoradiography revealed (R)-[(18)F]MH.MZ as a very selective and affine 5-HT2A tracer (K(i)=0.72 nM), whereas [(18)F]DD-1 showed no reasonable distribution pattern on autoradiographic sections. Moreover, results from microPET scans of (R)-[(18)F]MH.MZ hint on improved molecular imaging characteristics compared with those of [(18)F]MH.MZ. Therefore, (R)-[(18)F]MH.MZ appears to be a highly potent and selective serotonergic PET ligand in small animals.
- Addresses
- Clinical Research Group, Department of Psychiatry, Johannes Gutenberg University-Mainz, Untere Zahlbacher Strasse 8, 55131 Mainz, Germany.
- Autoren
- Fabian Debus
- Matthias M Herth
- Markus Piel
- Hans-Georg Buchholz
- Nicole Bausbacher
- Vasko Kramer
- Hartmut Lüddens
- Frank Rösch
- DOI
- 10.1016/j.nucmedbio.2010.02.002
- eISSN
- 1872-9614
- Externe Identifier
- PubMed Identifier: 20447561
- Open access
- false
- ISSN
- 0969-8051
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Nuclear medicine and biology
- Schlüsselwörter
- Animals
- Rats
- Rats, Sprague-Dawley
- Fluorine Radioisotopes
- Radioactive Tracers
- Fluorobenzenes
- Piperidines
- Receptor, Serotonin, 5-HT2A
- Positron-Emission Tomography
- Autoradiography
- Radiochemistry
- Male
- Molecular Imaging
- Serotonin 5-HT2 Receptor Antagonists
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2010
- Paginierung
- 487 - 495
- Datum der Veröffentlichung
- 2010
- Status
- Published
- Datum der Datenerfassung
- 2010
- Titel
- 18F-labeling and evaluation of novel MDL 100907 derivatives as potential 5-HT2A antagonists for molecular imaging.
- Sub types
- Research Support, Non-U.S. Gov't
- Journal Article
- Ausgabe der Zeitschrift
- 37
Data source: Europe PubMed Central
- Abstract
- INTRODUCTION: The serotonergic system, especially the 5-HT2A receptor, is involved in various diseases and conditions. It is a very interesting target for medicinal applications. METHODS: Two novel 5-HT2A tracers, namely, [(18)F]DD-1 and the enantiomeric pure (R)-[(18)F]MH.MZ, were radiolabeled by (18)F-fluoroalkylation of the corresponding desmethyl analogue. In vitro binding autoradiography on rat brain slices was performed to test the affinity and selectivity of these tracers. Moreover, first microPET experiments of (R)-[(18)F]MH.MZ were carried out in Sprague-Dawley rats. RESULTS: [(18)F]DD-1 (K(i)=3.23 nM) and (R)-[(18)F]MH.MZ (K(i)=0.72 nM) were (18)F-fluoroalkylated by the secondary synthon [(18)F]FETos in a radiochemical yield (RCY) of >70%. The final formulation for both tracers took no longer than 100 min with an overall RCY of approximately 40%. It provided [(18)F]tracers with a purity >96% and a typical specific activity of 25-35 GBq/mumol. Autoradiographic images of (R)-[(18)F]MH.MZ (5) and [(18)F]DD-1 (4) showed excellent visualization and selectivity of the 5-HT2A receptor for (R)-[(18)F]MH.MZ and less specific binding for [(18)F]DD-1. The binding potential (BP) of (R)-[(18)F]MH.MZ was determined to be 2.6 in the frontal cortex and 2.2 in the cortex (n=4), whereas the cortex-to-cerebellum ratio was determined to be 3.2 at steady state (n=4). Cortex-to-cerebellum ratios of (R)-[(18)F]MH.MZ were almost twice as much as compared with the racemic [(18)F]MH.MZ. Thereby, equal levels of specific activities were used. High uptake could be demonstrated in cortex regions. CONCLUSION: Labeling of both novel tracers was carried out in high RCY. Autoradiography revealed (R)-[(18)F]MH.MZ as a very selective and affine 5-HT2A tracer (K(i)=0.72 nM), whereas [(18)F]DD-1 showed no reasonable distribution pattern on autoradiographic sections. Moreover, results from microPET scans of (R)-[(18)F]MH.MZ hint on improved molecular imaging characteristics compared with those of [(18)F]MH.MZ. Therefore, (R)-[(18)F]MH.MZ appears to be a highly potent and selective serotonergic PET ligand in small animals.
- Date of acceptance
- 2010
- Autoren
- Fabian Debus
- Matthias M Herth
- Markus Piel
- Hans-Georg Buchholz
- Nicole Bausbacher
- Vasko Kramer
- Hartmut Lüddens
- Frank Rösch
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/20447561
- DOI
- 10.1016/j.nucmedbio.2010.02.002
- eISSN
- 1872-9614
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Nucl Med Biol
- Schlüsselwörter
- Animals
- Autoradiography
- Fluorine Radioisotopes
- Fluorobenzenes
- Male
- Molecular Imaging
- Piperidines
- Positron-Emission Tomography
- Radioactive Tracers
- Radiochemistry
- Rats
- Rats, Sprague-Dawley
- Receptor, Serotonin, 5-HT2A
- Serotonin 5-HT2 Receptor Antagonists
- Sprache
- eng
- Country
- United States
- Paginierung
- 487 - 495
- PII
- S0969-8051(10)00026-0
- Datum der Veröffentlichung
- 2010
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2010
- Titel
- 18F-labeling and evaluation of novel MDL 100907 derivatives as potential 5-HT2A antagonists for molecular imaging.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 37
Data source: PubMed
- Autoren
- Fabian Debus
- Matthias M Herth
- Markus Piel
- Hans-Georg Buchholz
- Nicole Bausbacher
- Vasko Kramer
- Hartmut Lüddens
- Frank Rösch
- Zeitschrift
- Nuclear medicine and biology
- Artikelnummer
- 4
- Paginierung
- 487 - 495
- Datum der Veröffentlichung
- 2010
- Herausgeber
- Elsevier
- Datum der Datenerfassung
- 2021
- Titel
- 18F-labeling and evaluation of novel MDL 100907 derivatives as potential 5-HT2A antagonists for molecular imaging
- Sub types
- article
- Ausgabe der Zeitschrift
- 37
Data source: Manual
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