Fluorodeoxyuridine improves imaging of human glioblastoma xenografts with radiolabeled iododeoxyuridine.

Details

Serval ID
serval:BIB_D0AD91A50F82
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Fluorodeoxyuridine improves imaging of human glioblastoma xenografts with radiolabeled iododeoxyuridine.
Journal
Cancer Research
Author(s)
Dupertuis Y.M., Vazquez M., Mach J.P., De Tribolet N., Pichard C., Slosman D.O., Buchegger F.
ISSN
0008-5472 (Print)
ISSN-L
0008-5472
Publication state
Published
Issued date
2001
Volume
61
Number
21
Pages
7971-7977
Language
english
Abstract
Use of radiolabeled nucleotides for tumor imaging is hampered by rapid in vivo degradation and low DNA-incorporation rates. We evaluated whether blocking of thymidine (dThd) synthesis by 5-fluoro-2'-deoxyuridine (FdUrd) could improve scintigraphy with radio-dThd analogues, such as 5-iodo-2'-deoxyuridine (IdUrd). We first show in vitro that coincubation with FdUrd substantially increased incorporation of [125I]IdUrd and [3H]dThd in the three tested human glioblastoma lines. Flow cytometry analysis showed that a short coincubation with FdUrd (1 h) produces a signal increase per labeled cell. We then measured biodistribution 24 h after i.v. injection of [125I]IdUrd in nude mice s.c. xenografted with the three glioblastoma lines. Compared with animals given [125I]IdUrd alone, i.v. preadministration for 1 h of 10 mg/kg FdUrd increased the uptake of [125I]IdUrd in the three tumors 4.8-6.8-fold. Compatible with previous reports, there were no side effects in mice observed for 2 months after receiving such a treatment. The tumor uptake of [125I]IdUrd was increased < or =13.6-fold when FdUrd preadministration was stepwise reduced to 1.1 mg/kg. Uptake increases remained lower (between 1.7- and 5.8-fold) in normal proliferating tissues (i.e., bone marrow, spleen, and intestine) and negligible in quiescent tissues. DNA extraction showed that 72-80% of radioactivity in tumor and intestine was bound to DNA. Scintigraphy of xenografted mice was performed at different times after i.v. injection of 3.7 MBq [125I]IdUrd. Tumor detection was significantly improved after FdUrd preadministration while still equivocal after 24 h in mice given [125I]IdUrd alone. Furthermore, background activity could be greatly reduced by p.o. administration of KClO4 in addition to potassium iodide. We conclude that FdUrd preadministration may improve positron or single photon emission tomography with cell division tracers, such as radio-IdUrd and possibly other dThd analogues.
Keywords
Animals, Brain Neoplasms/metabolism, Brain Neoplasms/pathology, Cell Cycle/drug effects, DNA, Neoplasm/metabolism, Drug Synergism, Floxuridine/pharmacology, Floxuridine/toxicity, Glioblastoma/metabolism, Glioblastoma/pathology, Humans, Idoxuridine/diagnostic use, Idoxuridine/pharmacokinetics, Iodine Radioisotopes/diagnostic use, Male, Mice, Mice, Nude, Perchloric Acid/pharmacology, Potassium Compounds/pharmacology, Radionuclide Imaging/methods, Radiopharmaceuticals/diagnostic use, Radiopharmaceuticals/pharmacokinetics, Thymidine/metabolism, Tissue Distribution, Tritium/diagnostic use, Tumor Cells, Cultured, Xenograft Model Antitumor Assays
Pubmed
Web of science
Create date
25/01/2008 11:27
Last modification date
20/08/2019 15:50
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