68Ga-Labelled Tropane Analogues for the Visualization of the Dopaminergic System |
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| Authors: | Dr. Sascha Häseli Marion Holy Dr. Markus Joksch Dr. Carina Bergner Dr. Andreas Wree Dr. Jens Kurth Aylin Cankaya Dr. Markus Piel Dr. Bernd J. Krause Dr. Harald H. Sitte Dr. Frank Rösch |
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| Affiliation: | 1. Institute of Nuclear Chemistry, Johannes Gutenberg-University Mainz, Fritz-Strassmann-Weg 2, 55128 Mainz, Germany;2. Institute of Pharmacology (Center for Physiology and Pharmacology), Medical University of Vienna, Währinger Straße 13a, 1090 Wien, Austria;3. Department of Nuclear Medicine, Rostock University Medical Center, Gertrudenplatz 1, 18057 Rostock, Germany;4. Institute of Anatomy, Rostock University Medical Center, Gertrudenstraße 9, 18057 Rostock, Germany |
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| 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. |
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| Keywords: | dopamine transporters gallium-68 imaging agents lipophilicity radiopharmaceuticals tropane |
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