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Fluorodeoxyuridine mediated cell cycle synchronization in S-phase increases the Auger radiation cell killing with 125I-iododeoxyuridine.
MedLine Citation:
PMID:  19795077     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
F Perillo-Adamer; M Kosinski; Y M Dupertuis; D Viertl; A Bischof Delaloye; F Buchegger
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Publication Detail:
Type:  Journal Article     Date:  2009-10-01
Journal Detail:
Title:  Nuklearmedizin. Nuclear medicine     Volume:  48     ISSN:  0029-5566     ISO Abbreviation:  Nuklearmedizin     Publication Date:  2009  
Date Detail:
Created Date:  2009-12-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7609387     Medline TA:  Nuklearmedizin     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  233-42     Citation Subset:  IM    
Affiliation:
Franz Buchegger, Service of Nuclear Medicine, University Hospital, Rue du Bugnon 46, 1011 Lausanne, SwitzerlandTel. +41/21/314 43 73, Fax +41/21/314 43 49 E-mail: Franz.Buchegger@chuv.ch.
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