Short fluorodeoxyuridine exposure of different human glioblastoma lines induces high-level accumulation of S-phase cells that avidly incorporate 125I-iododeoxyuridine.
- Perillo-Adamer F Service of Nuclear Medicine, University Hospital of Lausanne, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland. Florence.Adamer@chuv.ch
- Delaloye AB
- Genton CS
- Schaffland AO
- Dupertuis YM
- Buchegger F
- 2006-02-02
Published in:
- European journal of nuclear medicine and molecular imaging. - 2006
Cell Cycle
Cell Line, Tumor
Dose-Response Relationship, Drug
Floxuridine
Glioblastoma
Humans
Idoxuridine
Iodine Radioisotopes
Metabolic Clearance Rate
Radiopharmaceuticals
English
PURPOSE
Radio-iododeoxyuridine (IdUrd) is a potential Auger radiation therapy agent incorporated into DNA during the synthesis phase. In this study we sought to optimise S-phase targeting by modulating cellular cycling and radio-IdUrd DNA incorporation using short non-toxic fluorodeoxyuridine (FdUrd) incubations.
METHODS
Three human glioblastoma cell lines with different p53 expression were pre-treated with various FdUrd conditions. After different intervals, (125)I-IdUrd DNA incorporation was measured. Fluorescence-activated cell sorter cell cycle analysis was performed after identical intervals post FdUrd pre-treatment.
RESULTS
The highest increase in (125)I-IdUrd DNA incorporation was induced by 1-h incubation with 1 muM FdUrd. Increase in radio-IdUrd DNA incorporation was greatest 16-24 h after FdUrd, reaching factors of >or=7.5 over baseline incorporation in the three cell lines. Furthermore, cell synchronisation in S phase was observed with a peak of >or=69.5% in the three cell lines at 16 and 24 h post FdUrd, corresponding to an increase of 2.5-4.1 over baseline.
CONCLUSION
FdUrd-induced thymidine synthesis inhibition led to S-phase accumulation that was maximal after an interval of 16-24 h and time-correlated with the highest radio-IdUrd DNA incorporation. These observations might allow the rational design of an Auger radiation therapy targeting a maximal number of S-phase cells in single treatment cycles.
Radio-iododeoxyuridine (IdUrd) is a potential Auger radiation therapy agent incorporated into DNA during the synthesis phase. In this study we sought to optimise S-phase targeting by modulating cellular cycling and radio-IdUrd DNA incorporation using short non-toxic fluorodeoxyuridine (FdUrd) incubations.
METHODS
Three human glioblastoma cell lines with different p53 expression were pre-treated with various FdUrd conditions. After different intervals, (125)I-IdUrd DNA incorporation was measured. Fluorescence-activated cell sorter cell cycle analysis was performed after identical intervals post FdUrd pre-treatment.
RESULTS
The highest increase in (125)I-IdUrd DNA incorporation was induced by 1-h incubation with 1 muM FdUrd. Increase in radio-IdUrd DNA incorporation was greatest 16-24 h after FdUrd, reaching factors of >or=7.5 over baseline incorporation in the three cell lines. Furthermore, cell synchronisation in S phase was observed with a peak of >or=69.5% in the three cell lines at 16 and 24 h post FdUrd, corresponding to an increase of 2.5-4.1 over baseline.
CONCLUSION
FdUrd-induced thymidine synthesis inhibition led to S-phase accumulation that was maximal after an interval of 16-24 h and time-correlated with the highest radio-IdUrd DNA incorporation. These observations might allow the rational design of an Auger radiation therapy targeting a maximal number of S-phase cells in single treatment cycles.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1007/s00259-005-0009-y
- PMID 16450135
- Persistent URL
- https://sonar.ch/global/documents/139367
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