Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7977
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dc.contributor.authorGraf, Franziska-
dc.contributor.authorFahrer, Jörg-
dc.contributor.authorMaus, Stephan-
dc.contributor.authorMorgenstern, Alfred-
dc.contributor.authorBruchertseifer, Frank-
dc.contributor.authorVenkatachalam, Senthil-
dc.contributor.authorFottner, Christian-
dc.contributor.authorWeber, Matthias M.-
dc.contributor.authorHuelsenbeck, Johannes-
dc.contributor.authorSchreckenberger, Mathias-
dc.contributor.authorKaina, Bernd-
dc.contributor.authorMiederer, Matthias-
dc.date.accessioned2022-10-13T09:21:22Z-
dc.date.available2022-10-13T09:21:22Z-
dc.date.issued2014
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/7992-
dc.description.abstractRationale Key biologic effects of the alpha-particle emitter Actinium-225 in comparison to the beta-particle emitter Lutetium-177 labeled somatostatin-analogue DOTATOC in vitro and in vivo were studied to evaluate the significance of γH2AX-foci formation. Methods To determine the relative biological effectiveness (RBE) between the two isotopes (as - biological consequence of different ionisation-densities along a particle-track), somatostatin expressing AR42J cells were incubated with Ac-225-DOTATOC and Lu-177-DOTATOC up to 48 h and viability was analyzed using the MTT assay. DNA double strand breaks (DSB) were quantified by immunofluorescence staining of γH2AX-foci. Cell cycle was analyzed by flow cytometry. In vivo uptake of both radiolabeled somatostatin-analogues into subcutaneously growing AR42J tumors and the number of cells displaying γH2AX-foci were measured. Therapeutic efficacy was assayed by monitoring tumor growth after treatment with activities estimated from in vitro cytotoxicity. Results Ac-225-DOTATOC resulted in ED50 values of 14 kBq/ml after 48 h, whereas Lu-177-DOTATOC displayed ED50 values of 10 MBq/ml. The number of DSB grew with increasing concentration of Ac-225-DOTATOC and similarly with Lu-177-DOTATOC when applying a factor of 700-fold higher activity compared to Ac-225. Already 24 h after incubation with 2.5–10 kBq/ml, Ac-225-DOTATOC cell-cycle studies showed up to a 60% increase in the percentage of tumor cells in G2/M phase. After 72 h an apoptotic subG1 peak was also detectable. Tumor uptake for both radio peptides at 48 h was identical (7.5%ID/g), though the overall number of cells with γH2AX-foci was higher in tumors treated with 48 kBq Ac-225-DOTATOC compared to tumors treated with 30 MBq Lu-177-DOTATOC (35% vs. 21%). Tumors with a volume of 0.34 ml reached delayed exponential tumor growth after 25 days (44 kBq Ac-225-DOTATOC) and after 21 days (34 MBq Lu-177-DOTATOC). Conclusion γH2AX-foci formation, triggered by beta- and alpha-irradiation, is an early key parameter in predicting response to internal radiotherapy.en_GB
dc.description.sponsorshipDFG, Open Access-Publizieren Universität Mainz / Universitätsmedizinde
dc.language.isoengde
dc.rightsCC BY*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleDNA double strand breaks as predictor of efficacy of the alpha-particle emitter Ac-225 and the electron emitter Lu-177 for somatostatin receptor targeted radiotherapyen_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-7977-
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titlePLoS onede
jgu.journal.volume9de
jgu.journal.issue2de
jgu.pages.alternativee88239de
jgu.publisher.year2014-
jgu.publisher.namePLoSde
jgu.publisher.placeLawrence, Kan.de
jgu.publisher.urihttp://dx.doi.org/10.1371/journal.pone.0088239de
jgu.publisher.issn1932-6203de
jgu.organisation.placeMainz-
jgu.identifier.pmid24516620
jgu.subject.ddccode610de
opus.date.modified2018-08-08T08:15:15Z
opus.subject.dfgcode00-000
opus.organisation.stringFB 04: Medizin: Institut für Toxikologiede_DE
opus.organisation.stringFB 04: Medizin: Klinik und Poliklinik für Nuklearmedizinde_DE
opus.organisation.stringFB 04: Medizin: I. Medizinische Klinik und Poliklinikde_DE
opus.identifier.opusid27325
opus.importsourcepubmed
opus.institute.number0414
opus.institute.number0422
opus.institute.number0425
opus.metadataonlyfalse
opus.type.contenttypeKeinede_DE
opus.type.contenttypeNoneen_EN
opus.affiliatedFahrer, Jörg
opus.affiliatedFottner, Christian
opus.affiliatedWeber, Matthias M.
opus.affiliatedSchreckenberger, Mathias
opus.affiliatedKaina, Bernd
opus.affiliatedMiederer, Matthias
jgu.publisher.doi10.1371/journal.pone.0088239de
jgu.organisation.rorhttps://ror.org/023b0x485-
Appears in collections:DFG-OA-Publizieren (2012 - 2017)

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