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DOI: 10.3413/nukmed-0247
Fluorodeoxyuridine mediated cell cycle synchronization in S-phase increases the Auger radiation cell killing with 125I-iododeoxyuridine
Fluordeoxyuridin synchronisiert Glioblastom zellen in der S-Phase und erhöht die zelltötende Wirkung der Auger-Strahlung von 125I-IoddeoxyuridinPublikationsverlauf
received:
09. März 2009
accepted in revised form:
11. September 2009
Publikationsdatum:
24. Januar 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00034924/200906/lookinside/thumbnails/10-3413-nukmed-0247_de-1.jpg)
Summary
Aim: 125I-iododeoxyuridine is a potential Auger radiation therapy agent. Its incorporation in DNA of proliferating cells is enhanced by fluorodeoxyuridine. Here, we evaluated therapeutic activities of 125I-iododeoxyuridine in an optimized fluorodeoxyuridine pre-treatment inducing S-phase synchronization. Methods: After S-phase synchronization by fluorodeoxyuridine, cells were treated with 125I-iododeoxyuridine. Apoptosis analysis and S-phase synchronization were studied by flow cytometry. Cell survival was determined by colony-forming assay. Based on measured growth parameters, the number of decays per cell that induced killing was extrapolated. Results: Treatment experiments showed that 72 to 91% of synchronized cells were killed after 0.8 and 8 kBq/ml 125I-iododeoxyuridine incubation, respectively. In controls, only 8 to 38% of cells were killed by corresponding 125I-iododeoxyuridine activities alone and even increasing the activity to 80 kBq/ml gave only 42 % killing. Duplicated treatment cycles or repeated fluorodeoxyuridine pre-treatment allowed enhancing cell killing to >95 % at 8 kBq/ml 125I-iododeoxyuridine. About 50 and 160 decays per S-phase cells in controls and S-phase synchronization, respectively, were responsible for the observed cell killing at 0.8 kBq/ml radio-iododeoxyuridine. Conclusion: These data show the successful application of fluorodeoxyuridine that provided increased 125I-iododeoxyuridine Auger radiation cell killing efficacy through S-phase synchronization and high DNA incorporation of radio-iododeoxyuridine.
Zusammenfassung
Ziel: 125I-Ioddeoxyuridin ist ein potenzielles Auger-Strahlentherapeutikum, dessen Einbau in die DNA sich teilender Zellen durch Fluorde-oxyuridin (FdUrd) erhöht wird. Wir untersuchten therapeutische Konzentrationen von 125I-Ioddeoxyuridin innerhalb eines optimalen Therapieschemas von FdUrd-induzierter S-Phasen-Synchronisierung von Glioblastomzellen. Material, Methoden: Apoptose und Zellphasen wurden mittels Flusszytometrie gemessen. Die Zellüberlebensrate wurde anhand des Kolonie-Wachstumstests ermittelt. Wir haben ebenfalls unter Therapie in parallelen Experimenten die Daten ermittelt, die uns erlaubten, die Anzahl von 125I-Zerfällen zu bestimmen, welche die Zellen abtöteten. Ergebnisse: Zwischen 72 und 91% der mit FdUrd synchronisierten Zellen wurden durch 0,8 und 8 kBq/ml 125I-Ioddeoxyuridin abgetötet. Nur gerade 8 bis 38% der Kontrollzellen wurden durch 125I-Ioddeoxyuridin allein zerstört und selbst Erhöhung auf 80 kBq/ml erhöhte die zytostatische Effizienz nur unwesentlich. Verdopplung der Behandlungszyklen oder Wiederholung der FdUrd-Vorbehandlung ergab eine erhöhte Zytotoxizität auf mehr als 95% bei 8 kBq 125I-Ioddeoxyuridin. Bei 0.8 kBq/ml Radio-Ioddeoxyuridin bewirkten ungefähr 50 radioaktive Auger-Zerfälle den therapeutischen Effekt in Kontrollzellen und 160 Auger-Zerfälle denjenigen in S-Phasen-synchronisierten Zellen, gut vereinbar mit publizierten Toxizitätswerten von DNA-eingebauten Auger-Zerfällen. Schlussfolgerung: Die Resultate zeigen die erfolgreiche Anwendung von FdUrd, das die 125I-Ioddeoxyuridin-Auger-Strahleneffizienz deutlich verstärkt, vermittelt durch S-Phasen-Synchronisierung und einen gesteigerten DNA-Einbau des Radio-Iod-deoxyuridins.
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