Journal Article

FZJ-2021-00203

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Radiosynthesis and evaluation of 18F-labeled dopamine D4-receptor ligands

Willmann, M.FZJ* ; Ermert, J. (Corresponding author)FZJ* ; Prante, O. ; Hübner, H. ; Gmeiner, P. ; Neumaier, B.FZJ*

2021
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: http://hdl.handle.net/2128/27199  doi:10.1016/j.nucmedbio.2020.07.004

Abstract: 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.

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Contributing Institute(s):

1. Nuklearchemie (INM-5)

Research Program(s):

1. 525 - Decoding Brain Organization and Dysfunction (POF4-525) (POF4-525)

Appears in the scientific report 2021

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