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Radiolabelled Oligonucleotides for Imaging of Gene Expression with PET

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Abstract:

Our understanding of altered patterns of gene expression being responsible for many diseases has been growing thanks to modern molecular biological methods. Today, these changes can only be identified when tissue samples are available. Therefore, a noninvasive method allowing us to monitor gene expression in vivo would be valuable, not only as a research tool, but also for patient stratification before treatment and for treatment follow-up.

Antisense oligonucleotides (ODN) have been considered to be suitable molecules to trace active genes in vivo, as well as to treat diseases by hybridising to its complementary messenger RNA (mRNA) sequence in the cells thereby preventing the synthesis of the peptide. However, the use of ODNs in the organisms are endangered by many hurdles such as physical barriers to pass and enzyme attack to be avoided. Positron emission tomography (PET) provides a most advanced in vivo imaging technology that allows the exploration of the fate of radionuclide-labelled antisense ODNs in the body; thereby providing information about biodistribution and quantitative accumulation in tissues to assess pharmacokinetic properties of ODNs. This kind of evaluation is important as part of the characterisation of antisense therapeutics but also as part of the development of antisense imaging agents.

This review provides a general summary about the antisense concept and displays the present status of the antisense imaging field with the major achievements and remaining challenges on the long journey towards accomplishing in vivo monitoring of gene expression using PET.

Keywords: Antisense oligonucleotides; Gene expression; In vivo hybridisation; Pharmacokinetics; Positron emission tomography; Radiolabelling

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986709789712844

Affiliations: Uppsala Imanet, P.O. Box 967, S-751 09 Uppsala, Sweden.

Publication date: November 1, 2009

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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