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dc.contributor.authorRitawidya, Rien
dc.contributor.authorWenzel, Barbara
dc.contributor.authorTeodoro, Rodrigo
dc.contributor.authorToussaint, Magali
dc.contributor.authorKranz, Mathias
dc.contributor.authorDeuther-Conrad, Winnie
dc.contributor.authorDukić-Stefanović, Sladjana
dc.contributor.authorLudwig, Friedrich-Alexander
dc.contributor.authorScheunemann, Matthias
dc.contributor.authorBrust, Peter
dc.date.accessioned2020-02-27T13:06:50Z
dc.date.available2020-02-27T13:06:50Z
dc.date.issued2019-11-15
dc.description.abstractA specific radioligand for the imaging of cyclic nucleotide phosphodiesterase 2A (PDE2A) via positron emission tomography (PET) would be helpful for research on the physiology and disease-related changes in the expression of this enzyme in the brain. In this report, the radiosynthesis of a novel PDE2A radioligand and the subsequent biological evaluation were described. Our prospective compound 1-(2-chloro-5-methoxy phenyl)-8-(2-fluoropyridin-4-yl)-3- methylbenzo[e]imidazo[5,1-c][1,2,4]triazine, benzoimidazotriazine (BIT1) (IC<sub>50</sub> PDE2A = 3.33 nM; 16-fold selectivity over PDE10A) was fluorine-18 labeled via aromatic nucleophilic substitution of the corresponding nitro precursor using the K[<sup>18</sup>F]F-K<sub>2.2.2</sub>-carbonate complex system. The new radioligand [<sup>18</sup>F]BIT1 was obtained with a high radiochemical yield (54 ± 2%, n = 3), a high radiochemical purity (≥99%), and high molar activities (155–175 GBq/μmol, n = 3). In vitro autoradiography on pig brain cryosections exhibited a heterogeneous spatial distribution of [<sup>18</sup>F]BIT1 corresponding to the known pattern of expression of PDE2A. The investigation of in vivo metabolism of [<sup>18</sup>F]BIT1 in a mouse revealed sufficient metabolic stability. PET studies in mouse exhibited a moderate brain uptake of [<sup>18</sup>F]BIT1 with a maximum standardized uptake value of ~0.7 at 5 min p.i. However, in vivo blocking studies revealed a non-target specific binding of [<sup>18</sup>F]BIT1. Therefore, further structural modifications are needed to improve target selectivity.en_US
dc.identifier.citationRitawidya, Wenzel, Teodoro, Toussaint, Kranz M, Deuther-Conrad, Dukić-Stefanović, Ludwig, Scheunemann, Brust. Radiosynthesis and biological investigation of a novel fluorine-18 labeled benzoimidazotriazine- based radioligand for the imaging of phosphodiesterase 2A with positron emission tomography. Molecules. 2019;24:4149(22):1-17en_US
dc.identifier.cristinIDFRIDAID 1757010
dc.identifier.doi10.3390/molecules24224149
dc.identifier.issn1420-3049
dc.identifier.urihttps://hdl.handle.net/10037/17540
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.relation.journalMolecules
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2019 The Author(s)en_US
dc.subjectVDP::Technology: 500::Medical technology: 620en_US
dc.subjectVDP::Teknologi: 500::Medisinsk teknologi: 620en_US
dc.subjectVDP::Medical disciplines: 700en_US
dc.subjectVDP::Medisinske Fag: 700en_US
dc.titleRadiosynthesis and biological investigation of a novel fluorine-18 labeled benzoimidazotriazine- based radioligand for the imaging of phosphodiesterase 2A with positron emission tomographyen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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