PMID: 11606881Oct 19, 2001Paper

Hybridization and cell uptake studies with radiolabelled antisense oligonucleotides

Nuclear Medicine Communications
M A Stalteri, S J Mather

Abstract

Radiolabelled antisense oligonucleotides have been proposed as radiopharmaceuticals for imaging changes in the level of gene expression in vivo. This paper describes a study of the uptake of radiolabelled oligonucleotides in cell lines expressing different levels of the target mRNA. A 15-mer phosphorodiester deoxyoligonucleotide antisense to c-myc was labelled with 99mTc and 32P. Hybridization and stability studies were performed in vitro. Cell uptake studies were carried out in a c-myc expressing transformed rat embryonic fibroblast cell-line, TGR-1, and a knock-out cell line HO15.19 which does not express c-myc. The oligonucleotides were efficiently labelled with both radionuclides and retained their ability to hybridize with their complementary mRNA when extracted from cell lines. The radiolabelled oligonucleotides were stable for a few hours in human serum. No statistically significant difference was found between the uptake of radioactivity by the two cell lines. Although able to bind efficiently to their target in cell-free systems, radiolabelled oligonucleotides may be prevented from performing effectively as radiopharmaceutical vectors by the barriers imposed by cell membranes and/or intracellular metabolism.

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Citations

Oct 7, 2004·Annals of Nuclear Medicine·Donald J Hnatowich, Kayoko Nakamura
Mar 7, 2009·European Journal of Radiology·Archana MukherjeeMathew L Thakur
Dec 4, 2004·Cancer Gene Therapy·Xiaohong OuAnren Kuang
Apr 21, 2004·Nuclear Medicine Communications·Stephen J Mather

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