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

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).