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


CONCLUSIONS
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.
Service of Nuclear Medicine, University Hospital, Rue du Bugnon 46, 1011 Lausanne, Switzerland.
F
F
Perillo-Adamer
M
M
Kosinski
Y M
YM
Dupertuis
D
D
Viertl
A
A
Bischof Delaloye
F
F
Buchegger
D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D048750:Cell Nucleus Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D005467:Floxuridine / Q000494:pharmacology*; D005909:Glioblastoma / Q000473:pathology* / Q000503:physiopathology / Q000532:radiotherapy*; D006801:Humans; D011829:Radiation Dosage
D005467:Floxuridine