000825301 001__ 825301
000825301 005__ 20210129225255.0
000825301 037__ $$aFZJ-2016-07765
000825301 041__ $$aEnglish
000825301 1001_ $$0P:(DE-Juel1)144953$$aCavani, Melanie$$b0
000825301 1112_ $$a21st International Symposium on Radiopharmaceutical Sciences$$cColumbia$$d2015-05-26 - 2015-05-31$$gISRS 2015$$wUSA
000825301 245__ $$aNew strategy of a two-step radiosynthesis of [F-18]fluoropyridine-based maleimide-containing prosthetic groups for labelling of peptides and proteins
000825301 260__ $$c2015
000825301 3367_ $$033$$2EndNote$$aConference Paper
000825301 3367_ $$2BibTeX$$aINPROCEEDINGS
000825301 3367_ $$2DRIVER$$aconferenceObject
000825301 3367_ $$2ORCID$$aCONFERENCE_POSTER
000825301 3367_ $$2DataCite$$aOutput Types/Conference Poster
000825301 3367_ $$0PUB:(DE-HGF)24$$2PUB:(DE-HGF)$$aPoster$$bposter$$mposter$$s1482346411_11197$$xPlenary/Keynote
000825301 520__ $$aObjectives The use of thiol-reactive groups allows the introduction of fluorine-18 in a peptide or protein with cysteine residues, and different radiofluorinated maleimide-containing prosthetic groups have been described in the literature. All compounds were, however, prepared by a two- or three-step synthesis with an overall reaction time of at least 70 minutes. The aim of this work was to improve the radiosynthesis of maleimide-containing compounds with reduced reaction steps by using a new synthetic route via protection of the maleimide function. This was first done here with the example of 1-[3-(2-[18F]fluoropyridin-3-oxy)propyl]pyrrol-2,5-dione ([18F]FPyME) which is usually prepared in three steps [1]. Methods The first step for the preparation of the precursor was a Williamson reaction to form the ether from 3-hydroxy-2-nitropyridine with 1,3-dibromopropane. In a parallel process maleimide was protected with 2,5-dimethylfurane via a Diels-Alder-reaction. These two products were combined by N-alkylation to form the precursor. The radiosynthesis includes the introduction of fluorine-18 by nucleophilic substitution of the nitro group followed by deprotection of the maleimide function (see fig. 1). The reaction steps were optimized with regard to temperature, time and solvents. Results The optimal conditions for the n.c.a. radiofluorination were identified at a temperature of 80 °C in DMSO and a reaction time of 5 minutes, resulting in a radiochemical yield of about 29 ± 3 %. At higher temperatures the deprotection of the precursor and the labelled compound come to the fore and thereby the decomposition of the unprotected maleimide occurs due to the basic reaction conditions. The deprotection step was quantitatively carried out within 15 minutes. [18F]FPyME was isolated by HPLC to provide the pure prosthetic group which was directly used for effective peptide labelling. The overall synthesis time was about 60 minutes and the overall radiochemical yield was about 20 %. Conclusions The described synthetic route provides the possibility to gain a variety of further [18F]fluoropyridine-based maleimide-containing compounds in two steps only. In addition, this method offers to be performed as one-pot synthesis. Acknowledgements  References [1] de Bruin B. et al. (2006) Bioconjugate Chem., 16, 406-420.
000825301 536__ $$0G:(DE-HGF)POF3-573$$a573 - Neuroimaging (POF3-573)$$cPOF3-573$$fPOF III$$x0
000825301 7001_ $$0P:(DE-Juel1)131810$$aBier, Dirk$$b1$$ufzj
000825301 7001_ $$0P:(DE-Juel1)131816$$aCoenen, Heinrich Hubert$$b2$$eCorresponding author$$ufzj
000825301 909CO $$ooai:juser.fz-juelich.de:825301$$pVDB
000825301 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)131810$$aForschungszentrum Jülich$$b1$$kFZJ
000825301 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)131816$$aForschungszentrum Jülich$$b2$$kFZJ
000825301 9131_ $$0G:(DE-HGF)POF3-573$$1G:(DE-HGF)POF3-570$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lDecoding the Human Brain$$vNeuroimaging$$x0
000825301 9141_ $$y2016
000825301 920__ $$lyes
000825301 9201_ $$0I:(DE-Juel1)INM-5-20090406$$kINM-5$$lNuklearchemie$$x0
000825301 980__ $$aposter
000825301 980__ $$aVDB
000825301 980__ $$aI:(DE-Juel1)INM-5-20090406
000825301 980__ $$aUNRESTRICTED