Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
68 Ga-Labelled Tropane Analogues for the Visualization of the Dopaminergic System
Ist Teil von
ChemMedChem, 2021-03, Vol.16 (5), p.804-808
Ort / Verlag
Germany
Erscheinungsjahr
2021
Link zum Volltext
Quelle
Wiley-Blackwell Journals
Beschreibungen/Notizen
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
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, [
Ga]Ga-HBED-hexadiyne-tropane, showed an IC
value of 66 nM, together with a log D
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.
Sprache
Englisch
Identifikatoren
ISSN: 1860-7179
eISSN: 1860-7187
DOI: 10.1002/cmdc.202000820
Titel-ID: cdi_proquest_miscellaneous_2465446539
Format
–
Weiterführende Literatur
Empfehlungen zum selben Thema automatisch vorgeschlagen von bX