Antisense oligonucleotides, in short antisense, are small chains of nucleic
acids capable to bind to cellular ribonucleic acid (RNA) by a hybridizatio
n mechanism. In vitro, antisense are widely used as reagents to detect or b
lock specific RNA sequences. The use of antisense as in vivo diagnostic age
nts is attractive because it would bring molecular imaging at the level of
gene expression However, oligonucleotides are non-canonical radio-pharmaceu
ticals and much progress is needed to adapt them to in vivo imaging. The re
quirements to reach this goal include improvements in radiosynthesis, stabi
lity, targeting, and specific and non-specific binding. They will be examin
ed in this review together with the current achievements In the application
s of antisense as nuclear medicine radiopharmaceuticals.