Unlabelled iododeoxyuridine increases the rate of uptake of [125I]iododeoxyuridine in human xenografted glioblastomas.
5-Iodo-2'-deoxyuridine (IdUrd), a thymidine (TdR) analogue, can be radiolabelled with iodine-125, an Auger radiation emitter, to provoke double-strand breaks once incorporated into DNA of cancer cells. We have previously shown that co-incubation of [125I]IdUrd with unlabelled IdUrd provided an additive cytotoxicity in two human glioblastoma cell lines. This observation was unexpectedly correlated with an increase in the rate of DNA incorporation of [125I]IdUrd. Here, we further evaluated the effects of unlabelled IdUrd on the uptake of [125I]IdUrd in vitro and in vivo in mice xenografted with three human glioblastoma lines. The results showed that, in these three glioblastoma lines, unlabelled IdUrd increased the rate of uptake of [125I]IdUrd in vitro by 2- to 4.4-fold and in vivo by 1.5- to 2.8-fold. The rate of uptake of [125I]IdUrd in normal rapidly dividing tissues was also increased by 1.3- to 2.8-fold. TdR completely blocked [125I]IdUrd uptake in tumours and tissues. Analogues of IdUrd, such as deoxyuridine and 5-iodo-1,3-dimethyuracil, did not reproduce the effect of IdUrd on the uptake of [125I]IdUrd, suggesting that it is not related to protection against [125I]IdUrd degradation. It is concluded that combined administration of unlabelled IdUrd may improve the use of radiolabelled IdUrd for cancer diagnosis or therapy.
Dupertuis
Yves M
YM
Clinical Nutrition, University Hospital of Geneva, Geneva, Switzerland. Yves.M.Dupertuis@hcuge.ch
Xiao
Wei-Hong
WH
De Tribolet
Nicolas
N
Pichard
Claude
C
Slosman
Daniel O
DO
Bischof Delaloye
Angelika
A
Buchegger
Franz
F
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007065:Idoxuridine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D051379:Mice; D008819:Mice, Nude; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D004273:DNA, Neoplasm; D007457:Iodine Radioisotopes; D019384:Nucleic Acid Synthesis Inhibitors; D007065:Idoxuridine