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The Evolution of Radionanotargeting towards Clinical Precision Oncology: A Festschrift in Honor of Kalevi Kairemo

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Introduction to Radionanotargeting in the 1990's: Dosimetry and Optimization of Antisense Oligonucleotide Radiotherapy in Vivo

Author(s): Antti Jekunen*, Mikko Tenhunen and Kalevi Kairemo

Pp: 32-39 (8)

DOI: 10.2174/9781681088655122010007

* (Excluding Mailing and Handling)

Abstract

Radiolabeled oligodeoxynucleotides (ODNs) have the potential of having
both direct antisense inhibition and radiation effects being derived against the most
specific target, a DNA/RNA sequence. Nuclear DNA is the primary target for ionizing
radiation, and low-energy electrons with short ranges are responsible for the
radiotoxicity of Auger electron emitters. Antisense technology has begun to provide an
alternative approach for manipulating the expression of specific genes. Here, we
optimize the label of ODNs with Auger-emitting radionuclides by calculating
subcellular dose distribution. We show that for subcellular targeting, internal labels 35S
and 32P give the lowest variation in estimated absorbed nuclear dose in our cell model
with defined dimensions (nuclear diameter, 6-16 μm ; cellular diameter, 12-20 μm).

Keywords: Antisense, Dosimetry, Oligonucleotide, Radionanotargeting.

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