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

• Published in: Nuclear medicine Vol. 48; no. 6; p. 233
• Main Authors: Perillo-Adamer, F, Kosinski, M, Dupertuis, Y M, Viertl, D, Bischof Delaloye, A, Buchegger, F
• Format: Journal Article
• Language: English
• Published: Germany 2009
• Subjects: Apoptosis - radiation effects; Cell Line, Tumor; Cell Nucleus Division - drug effects; Cell Nucleus Division - radiation effects; Cell Survival - radiation effects; Floxuridine - pharmacology; Glioblastoma - pathology; Glioblastoma - physiopathology; Glioblastoma - radiotherapy; Humans; Radiation Dosage
• ISSN: 0029-5566
• DOI: 10.3413/nukmed-0247

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. 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. 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. 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.