68Ga-Labelled Tropane Analogues for the Visualization of the Dopaminergic System
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Sascha Haeseli
- Marion Holy
- Markus Joksch
- Carina Bergner
- Andreas Wree
- Jens Kurth
- Aylin Cankaya
- Markus Piel
- Bernd J Krause
- Harald H Sitte
- Frank Roesch
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000597680500001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1002/cmdc.202000820
- eISSN
- 1860-7187
- Externe Identifier
- Clarivate Analytics Document Solution ID: QQ5PE
- PubMed Identifier: 33245194
- ISSN
- 1860-7179
- Ausgabe der Veröffentlichung
- 5
- Zeitschrift
- CHEMMEDCHEM
- Schlüsselwörter
- dopamine transporters
- gallium-68
- imaging agents
- lipophilicity
- radiopharmaceuticals
- tropane
- Paginierung
- 804 - 808
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Titel
- <SUP>68</SUP>Ga-Labelled Tropane Analogues for the Visualization of the Dopaminergic System
- Sub types
- Article
- Ausgabe der Zeitschrift
- 16
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Abstract
- <jats:title>Abstract</jats:title><jats:p>The development of radiometal‐labelled pharmaceuticals for neuroimaging could offer great potential due to easier handling during labelling and availability through radionuclide generator systems. Nonetheless, to date, no such tracers are available for positron emission tomography, primarily owing to the challenge of crossing the blood–brain barrier (BBB) and loss of affinity through chelator attachment. We have prepared a variety of <jats:sup>68</jats:sup>Ga‐labelled phenyltropanes showing that, through a simple hydrocarbon‐linker, it is possible to introduce a chelator onto the lead structure while maintaining its high affinity for hDAT (human dopamine transporter) and simultaneously achieving adequate lipophilicity. One of the candidates, [<jats:sup>68</jats:sup>Ga]Ga‐HBED‐hexadiyne‐tropane, showed an IC<jats:sub>50</jats:sub> value of 66 nM, together with a log <jats:italic>D</jats:italic><jats:sub>7.4</jats:sub> of 0.96. A μPET study in a hemi‐parkinsonian rat model showed a fast wash‐out of the tracer, and no specific uptake in the brain, thus implying an inability to penetrate the BBB.</jats:p>
- Autoren
- Sascha Häseli
- Marion Holy
- Markus Joksch
- Carina Bergner
- Andreas Wree
- Jens Kurth
- Aylin Cankaya
- Markus Piel
- Bernd J Krause
- Harald H Sitte
- Frank Rösch
- DOI
- 10.1002/cmdc.202000820
- eISSN
- 1860-7187
- ISSN
- 1860-7179
- Ausgabe der Veröffentlichung
- 5
- Zeitschrift
- ChemMedChem
- Sprache
- en
- Online publication date
- 2020
- Paginierung
- 804 - 808
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Herausgeber
- Wiley
- Herausgeber URL
- http://dx.doi.org/10.1002/cmdc.202000820
- Datum der Datenerfassung
- 2023
- Titel
- <sup>68</sup>Ga‐Labelled Tropane Analogues for the Visualization of the Dopaminergic System
- Ausgabe der Zeitschrift
- 16
Datenquelle: Crossref
- Abstract
- The development of radiometal-labelled pharmaceuticals for neuroimaging could offer great potential due to easier handling during labelling and availability through radionuclide generator systems. Nonetheless, to date, no such tracers are available for positron emission tomography, primarily owing to the challenge of crossing the blood-brain barrier (BBB) and loss of affinity through chelator attachment. We have prepared a variety of <sup>68</sup> Ga-labelled phenyltropanes showing that, through a simple hydrocarbon-linker, it is possible to introduce a chelator onto the lead structure while maintaining its high affinity for hDAT (human dopamine transporter) and simultaneously achieving adequate lipophilicity. One of the candidates, [<sup>68</sup> Ga]Ga-HBED-hexadiyne-tropane, showed an IC<sub>50</sub> value of 66 nM, together with a log D<sub>7.4</sub> of 0.96. A μPET study in a hemi-parkinsonian rat model showed a fast wash-out of the tracer, and no specific uptake in the brain, thus implying an inability to penetrate the BBB.
- Addresses
- Institute of Nuclear Chemistry, Johannes Gutenberg-University Mainz, Fritz-Strassmann-Weg 2, 55128, Mainz, Germany.
- Autoren
- Sascha Häseli
- Marion Holy
- Markus Joksch
- Carina Bergner
- Andreas Wree
- Jens Kurth
- Aylin Cankaya
- Markus Piel
- Bernd J Krause
- Harald H Sitte
- Frank Rösch
- DOI
- 10.1002/cmdc.202000820
- eISSN
- 1860-7187
- Externe Identifier
- PubMed Identifier: 33245194
- PubMed Central ID: PMC7984292
- Funding acknowledgements
- Viennese Fund for Science and Technology: CS15-033
- Open access
- true
- ISSN
- 1860-7179
- Ausgabe der Veröffentlichung
- 5
- Zeitschrift
- ChemMedChem
- Schlüsselwörter
- Blood-Brain Barrier
- Animals
- Rats
- Rats, Wistar
- Gallium Radioisotopes
- Tropanes
- Radiopharmaceuticals
- Positron-Emission Tomography
- Molecular Structure
- Structure-Activity Relationship
- Dose-Response Relationship, Drug
- Male
- Dopamine Plasma Membrane Transport Proteins
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2020
- Open access status
- Open Access
- Paginierung
- 804 - 808
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Publisher licence
- CC BY-NC-ND
- Datum der Datenerfassung
- 2020
- Titel
- <sup>68</sup> Ga-Labelled Tropane Analogues for the Visualization of the Dopaminergic System.
- Sub types
- Research Support, Non-U.S. Gov't
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 16
Files
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cmdc.202000820 https://europepmc.org/articles/PMC7984292?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- The development of radiometal-labelled pharmaceuticals for neuroimaging could offer great potential due to easier handling during labelling and availability through radionuclide generator systems. Nonetheless, to date, no such tracers are available for positron emission tomography, primarily owing to the challenge of crossing the blood-brain barrier (BBB) and loss of affinity through chelator attachment. We have prepared a variety of 68 Ga-labelled phenyltropanes showing that, through a simple hydrocarbon-linker, it is possible to introduce a chelator onto the lead structure while maintaining its high affinity for hDAT (human dopamine transporter) and simultaneously achieving adequate lipophilicity. One of the candidates, [68 Ga]Ga-HBED-hexadiyne-tropane, showed an IC50 value of 66 nM, together with a log D7.4 of 0.96. A μPET study in a hemi-parkinsonian rat model showed a fast wash-out of the tracer, and no specific uptake in the brain, thus implying an inability to penetrate the BBB.
- Autoren
- Sascha Häseli
- Marion Holy
- Markus Joksch
- Carina Bergner
- Andreas Wree
- Jens Kurth
- Aylin Cankaya
- Markus Piel
- Bernd J Krause
- Harald H Sitte
- Frank Rösch
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/33245194
- DOI
- 10.1002/cmdc.202000820
- eISSN
- 1860-7187
- Externe Identifier
- PubMed Central ID: PMC7984292
- Funding acknowledgements
- Viennese Fund for Science and Technology: CS15-033
- Ausgabe der Veröffentlichung
- 5
- Zeitschrift
- ChemMedChem
- Schlüsselwörter
- dopamine transporters
- gallium-68
- imaging agents
- lipophilicity
- radiopharmaceuticals
- tropane
- Animals
- Blood-Brain Barrier
- Dopamine Plasma Membrane Transport Proteins
- Dose-Response Relationship, Drug
- Gallium Radioisotopes
- Male
- Molecular Structure
- Positron-Emission Tomography
- Radiopharmaceuticals
- Rats
- Rats, Wistar
- Structure-Activity Relationship
- Tropanes
- Sprache
- eng
- Country
- Germany
- Paginierung
- 804 - 808
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2021
- Titel
- 68 Ga-Labelled Tropane Analogues for the Visualization of the Dopaminergic System.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 16
Datenquelle: PubMed
- Author's licence
- CC-BY-NC-ND
- Autoren
- Sascha Häseli
- Marion Holy
- Markus Joksch
- Carina Bergner
- Andreas Wree
- Jens Kurth
- Aylin Cankaya
- Markus Piel
- Bernd J Krause
- Harald H Sitte
- Frank Rösch
- Hosting institution
- Universitätsbibliothek Mainz
- Sammlungen
- JGU-Publikationen
- Resource version
- Published version
- DOI
- 10.1002/cmdc.202000820
- File(s) embargoed
- false
- Open access
- true
- ISSN
- 1860-7187
- Ausgabe der Veröffentlichung
- 5
- Zeitschrift
- ChemMedChem
- Schlüsselwörter
- 540 Chemie
- 540 Chemistry and allied sciences
- Sprache
- eng
- Open access status
- Open Access
- Paginierung
- 804 - 808
- Datum der Veröffentlichung
- 2021
- Public URL
- https://openscience.ub.uni-mainz.de/handle/20.500.12030/6029
- Herausgeber
- Wiley-VCH
- Herausgeber URL
- https://doi.org/10.1002/cmdc.202000820
- Datum der Datenerfassung
- 2021
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2021
- Zugang
- Public
- Titel
- 68Ga-labelled tropane analogues for the visualization of the dopaminergic system
- Ausgabe der Zeitschrift
- 16
Files
häseli_sascha-68ga-labelled_-20210607170749196.pdf
Datenquelle: OPENSCIENCE.UB
- Beziehungen:
- Eigentum von