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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
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
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY-NC-ND
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Journal: ChemMedChem
Pages or article number: 804
Publisher: Wiley-VCH
Publisher place: Weinheim u.a.
Issue date: 2021
ISSN: 1860-7187
Publisher URL:
Publisher DOI: 10.1002/cmdc.202000820
Appears in collections:JGU-Publikationen

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