TY  - JOUR
AU  - Willmann, Michael
AU  - Ermert, Johannes
AU  - Prante, Olaf
AU  - Hübner, Harald
AU  - Gmeiner, Peter
AU  - Neumaier, Bernd
TI  - Radiosynthesis and evaluation of 18F-labeled dopamine D4-receptor ligands
JO  - Nuclear medicine and biology
VL  - 92
SN  - 0969-8051
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - FZJ-2021-00203
SP  - 43-52
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 32718750
UR  - <Go to ISI:>//WOS:000616652500006
DO  - DOI:10.1016/j.nucmedbio.2020.07.004
UR  - https://juser.fz-juelich.de/record/889311
ER  -