Unlabelled iododeoxyuridine increases the rate of uptake of [125I]iododeoxyuridine in human xenografted glioblastomas

European Journal of Nuclear Medicine and Molecular Imaging
Y M DupertuisFranz Buchegger

Abstract

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 administr...Continue Reading

Citations

Jun 18, 2010·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·David ViertlFranz Buchegger
Apr 23, 2013·Nuclear Medicine and Biology·Anna Rita CervinoLaura Evangelista
Jun 16, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Philippe A CouckeHuu Phuoc Do

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