%0 Journal Article
%A Willmann, Michael
%A Ermert, Johannes
%A Prante, Olaf
%A Hübner, Harald
%A Gmeiner, Peter
%A Neumaier, Bernd
%T Radiosynthesis and evaluation of 18F-labeled dopamine D4-receptor ligands
%J Nuclear medicine and biology
%V 92
%@ 0969-8051
%C Amsterdam [u.a.]
%I Elsevier Science
%M FZJ-2021-00203
%P 43-52
%D 2021
%X IntroductionThe dopamine D4 receptor (D4R) has attracted considerable attention as potential target for the treatment of a broad range of central nervous system disorders. Although many efforts have been made to improve the performance of putative radioligand candidates, there is still a lack of D4R selective tracers suitable for in vivo PET imaging. Thus, the objective of this work was to develop a D4-selective PET ligand for clinical applications.MethodsFour compounds based on previous and new lead structures were prepared and characterized with regard to their D4R subtype selectivity and predicted lipophilicity. From these, 3-((4-(2-fluorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo[2,3-b]pyridine I and (S)-4-(3-fluoro-4-methoxybenzyl)-2-(phenoxymethyl)morpholine II were selected for labeling with fluorine-18 and subsequent evaluation by in vitro autoradiography to assess their suitability as D4 radioligand candidates for in vivo imaging.ResultsThe radiosynthesis of [18F]I and [18F]II was successfully achieved by copper-mediated radiofluorination with radiochemical yields of 7% and 66%, respectively. The radioligand [18F]II showed specific binding in areas where D4 expression is expected, whereas [18F]I did not show any uptake in distinct brain regions and exhibited an unacceptable degree of non-specific binding.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ 32718750
%U <Go to ISI:>//WOS:000616652500006
%R 10.1016/j.nucmedbio.2020.07.004
%U https://juser.fz-juelich.de/record/889311