Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-6020
Authors: | Häseli, Sascha Holy, Marion Joksch, Markus Bergner, Carina Wree, Andreas Kurth, Jens Cankaya, Aylin Piel, Markus Krause, Bernd J. Sitte, Harald H. Rösch, Frank |
Title: | 68Ga-labelled tropane analogues for the visualization of the dopaminergic system |
Online publication date: | 25-Jun-2021 |
Year of first publication: | 2021 |
Language: | english |
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 68Ga-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, [68Ga]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. |
DDC: | 540 Chemie 540 Chemistry and allied sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 09 Chemie, Pharmazie u. Geowissensch. |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-6020 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
License: | CC BY-NC-ND |
Information on rights of use: | https://creativecommons.org/licenses/by-nc-nd/4.0/ |
Journal: | ChemMedChem 16 5 |
Pages or article number: | 804 808 |
Publisher: | Wiley-VCH |
Publisher place: | Weinheim u.a. |
Issue date: | 2021 |
ISSN: | 1860-7187 |
Publisher URL: | https://doi.org/10.1002/cmdc.202000820 |
Publisher DOI: | 10.1002/cmdc.202000820 |
Appears in collections: | JGU-Publikationen |
Files in This Item:
File | Description | Size | Format | ||
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häseli_sascha-68ga-labelled_-20210607170749196.pdf | 1.24 MB | Adobe PDF | View/Open |