Description: Radiosynthesis and evaluation of 18F-labeled dopamine D4-receptor ligands

This title appears in the Scientific Report : 2021

Radiosynthesis and evaluation of 18F-labeled dopamine D4-receptor ligands

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...

Personal Name(s):	Willmann, Michael
	Ermert, Johannes (Corresponding author) / Prante, Olaf / Hübner, Harald / Gmeiner, Peter / Neumaier, Bernd
Contributing Institute:	Nuklearchemie; INM-5
Published in:	Nuclear medicine and biology, 92 (2021) S. 43-52
Imprint:	Amsterdam [u.a.] Elsevier Science 2021
DOI:	10.1016/j.nucmedbio.2020.07.004
Document Type:	Journal Article
Research Program:	Decoding Brain Organization and Dysfunction
Link:	Get full text Get full text Published on 2020-07-16. Available in OpenAccess from 2021-07-16.
	Publikationsportal JuSER

Please use the identifier: http://hdl.handle.net/2128/27199 in citations.
Please use the identifier: http://dx.doi.org/10.1016/j.nucmedbio.2020.07.004 in citations.

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.