Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7442
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dc.contributor.authorSchieferstein, Hanno-
dc.contributor.authorBetzel, Thomas-
dc.contributor.authorFischer, Cindy R.-
dc.contributor.authorRoss, Tobias-
dc.date.accessioned2022-07-15T10:02:25Z-
dc.date.available2022-07-15T10:02:25Z-
dc.date.issued2013-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/7456-
dc.description.abstractBackground The folate receptor (FR) is a well-established target for tumor imaging and therapy. To date, only a few 18 F-folate conjugates via 18 F-prosthetic group labeling for positron emission tomography (PET) imaging have been developed. To some extent, they all lack the optimal balance between efficient radiochemistry and favorable in vivo characteristics. Methods A new clickable olate precursor was synthesized by regioselective coupling of folic acid to 11-azido-3,6,9-trioxaundecan-1-amine at the γ-position of the glutamic acid residue. The non-radioactive reference compound was synthesized via copper-catalyzed azide-alkyne cycloaddition of 3-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)prop-1-yne and γ-(11-azido-3,6,9-trioxaundecanyl)folic acid amide. The radiosynthesis was accomplished in two steps: at first a 18 F-fluorination of 2-(2-(2-(prop-2-yn-1-yloxy)ethoxy)ethoxy)ethyl-4-methylbenzenesulfonate, followed by a 18 F-click reaction with the γ-azido folate. The in vitro, ex vivo, and in vivo behaviors of the new 18 F-folate were investigated using FR-positive human KB cells in displacement assays and microPET studies using KB tumor-bearing mice. Results The new 18 F-folate with oligoethylene spacers showed reduced lipophilicity in respect to the previously developed 18 F-click folate with alkyl spacers and excellent affinity (Ki = 1.6 nM) to the FR. Combining the highly efficient 18 F-click chemistry and a polar oligoethylene-based 18 F-prosthetic group facilitated these results. The overall radiochemical yield of the isolated and formulated product averages 8.7%. In vivo PET imaging in KB tumor-bearing mice showed a tumor uptake of 3.4% ID/g tissue, which could be reduced by FR blockade with native folic acid. Although the new 18 F-oligoethyleneglycole (OEG)-folate showed reduced hepatobiliary excretion over time, a distinct unspecific abdominal background was still observed. Conclusions A new 18 F-folate was developed, being available in very high radiochemical yields via a fast and convenient two-step radiosynthesis. The new 18 F-OEG-folate showed good in vivo behavior and lines up with several recently evaluated 18 F-labeled folates.en_GB
dc.description.sponsorshipDFG, Open Access-Publizieren Universität Mainz / Universitätsmedizinde
dc.language.isoengde
dc.rightsCC BY*
dc.rights.urihttps://creativecommons.org/licenses/by/2.0/*
dc.subject.ddc540 Chemiede_DE
dc.subject.ddc540 Chemistry and allied sciencesen_GB
dc.title18F-click labeling and preclinical evaluation of a new 18F-folate for PET imagingen_GB
dc.title.alternative<sup>18</sup>F-click labeling and preclinical evaluation of a new <sup>18</sup>F-folate for PET imagingde_DE
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-7442-
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 09 Chemie, Pharmazie u. Geowissensch.de
jgu.organisation.number7950-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleEJNMMI Researchde
jgu.journal.volume3de
jgu.pages.alternativeArt. 68de
jgu.publisher.year2013-
jgu.publisher.nameSpringerde
jgu.publisher.placeBerlinde
jgu.publisher.urihttp://dx.doi.org/10.1186/2191-219X-3-68de
jgu.publisher.issn2191-219Xde
jgu.organisation.placeMainz-
jgu.subject.ddccode540de
opus.date.modified2018-08-06T10:29:49Z-
opus.subject.dfgcode06-301-
opus.organisation.stringFB 09: Chemie, Pharmazie und Geowissenschaften: Institut für Kernchemiede_DE
opus.identifier.opusid24291-
opus.institute.number0904-
opus.metadataonlyfalse-
opus.type.contenttypeKeinede_DE
opus.type.contenttypeNoneen_EN
opus.affiliatedSchieferstein, Hanno-
opus.affiliatedRoss, Tobias-
jgu.publisher.doi10.1186/2191-219X-3-68de
jgu.organisation.rorhttps://ror.org/023b0x485-
Appears in collections:DFG-OA-Publizieren (2012 - 2017)

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