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Fluorodeoxyuridine mediated cell cycle synchronization in S-phase increases the Auger radiation cell killing with 125I-iododeoxyuridine

Perillo-Adamer, F.
Kosinski, M.
Viertl, D.
Bischof Delaloye, A.
Published in Nuklearmedizin. 2009, vol. 48, no. 6, p. 233-242
Abstract 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.
Keywords Apoptosis/radiation effectsCell Line, TumorCell Nucleus Division/drug effects/radiation effectsCell Survival/radiation effectsFloxuridine/*pharmacologyGlioblastoma/*pathology/physiopathology/*radiotherapyHumansRadiation Dosage
PMID: 19795077
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Research group Ciblage tumoral par anticorps, peptides et nucléotides radiomarqués (221)
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PERILLO-ADAMER, F. et al. Fluorodeoxyuridine mediated cell cycle synchronization in S-phase increases the Auger radiation cell killing with 125I-iododeoxyuridine. In: Nuklearmedizin, 2009, vol. 48, n° 6, p. 233-242. https://archive-ouverte.unige.ch/unige:19568

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Deposited on : 2012-04-23

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