Fluorodeoxyuridine improves imaging of human glioblastoma xenografts with radiolabeled iododeoxyuridine

Article Article scientifique Article Fluorodeoxyuridine improves imaging of human glioblastoma xenografts with radiolabeled iododeoxyuridine eng 2001 author Dupertuis Yves Marc 0000-0003-4891-0487 24489 author Vazquez Maria Dolores 501453 author Mach Jean-Pierre author De Tribolet Nicolas 29973 author Pichard Claude 21908 author Slosman Daniel 28416 author Buchegger Franz 124544 7971-7977 11691821 0008-5472 https://cancerres.aacrjournals.org/content/61/21/7971.long 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. Animals Brain Neoplasms/diagnostic imaging/metabolism/pathology Cell Cycle/drug effects DNA, Neoplasm/metabolism Drug Synergism Floxuridine/pharmacology/toxicity Glioblastoma/diagnostic imaging/metabolism/pathology Humans Idoxuridine/pharmacokinetics/toxicity Iodine Radioisotopes Male Mice Mice, Nude Perchlorates/pharmacology Potassium Compounds/pharmacology Radionuclide Imaging/methods Radiopharmaceuticals/pharmacokinetics/toxicity Thymidine/metabolism Tissue Distribution Tritium Tumor Cells, Cultured Xenograft Model Antitumor Assays Dewey 616 Dewey 617 Swiss National Science Foundation 31-47 204.96 CH 56 Département de médecine 221 57 Département de chirurgie 222 false Cancer Research 61 21 7185574c-e06c-45b6-a026-887828e2c387 Article (Published version) Public DupertuisYMCancerRes2001.pdf 182365 application/pdf openAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département de chirurgie

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Fluorodeoxyuridine improves imaging of human glioblastoma xenografts with radiolabeled iododeoxyuridine	Cancer Research			2001	261	187

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Vazquez, Maria Dolores